=== Generating (published_papers) ===
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==== begin registerFile(/WWW/pub2/data/ERD/person/140706/researchmap/published_papers.jsonl) ====
line:1, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117592","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/34978525","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=388677","label":"url"}],"paper_title":{"en":"The first non-prion pathogen identified: neurotropic influenza virus.","ja":"The first non-prion pathogen identified: neurotropic influenza virus."},"authors":{"en":[{"name":"Sakaguchi Suehiro"},{"name":"Hara Hideyuki"}],"ja":[{"name":"坂口 末廣"},{"name":"原 英之"}]},"publication_date":"2022-12","publication_name":{"en":"Prion","ja":"Prion"},"volume":"Vol.16","number":"No.1","starting_page":"1","ending_page":"6","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1080/19336896.2021.2015224"],"issn":["1933-690X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:2, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/35973512","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=401533","label":"url"}],"paper_title":{"en":"Central residues in prion protein PrPC are crucial for its conversion into the pathogenic isoform","ja":"Central residues in prion protein PrPC are crucial for its conversion into the pathogenic isoform"},"authors":{"en":[{"name":"Pasiana Agriani Dini"},{"name":"Miyata Hironori"},{"name":"Chida Junji"},{"name":"Hara Hideyuki"},{"name":"Imamura Morikazu"},{"name":"Atarashi Ryuichiro"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"Pasiana Agriani Dini"},{"name":"Miyata Hironori"},{"name":"千田 淳司"},{"name":"原 英之"},{"name":"Imamura Morikazu"},{"name":"Atarashi Ryuichiro"},{"name":"坂口 末廣"}]},"publication_date":"2022-08-13","publication_name":{"en":"The Journal of Biological Chemistry","ja":"The Journal of Biological Chemistry"},"volume":"Vol.298","number":"No.9","starting_page":"102381","ending_page":"102381","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.jbc.2022.102381"],"issn":["1083-351X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:3, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117550","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/34830321","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=388676","label":"url"}],"paper_title":{"en":"Virus Infection, Genetic Mutations, and Prion Infection in Prion Protein Conversion.","ja":"Virus Infection, Genetic Mutations, and Prion Infection in Prion Protein Conversion."},"authors":{"en":[{"name":"Hara Hideyuki"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"原 英之"},{"name":"坂口 末廣"}]},"publication_date":"2021-11-18","publication_name":{"en":"International Journal of Molecular Sciences","ja":"International Journal of Molecular Sciences"},"volume":"Vol.22","number":"No.22","starting_page":"12439","ending_page":"12439","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3390/ijms222212439"],"issn":["1422-0067"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:4, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117551","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/34769172","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85118175726&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=388671","label":"url"}],"paper_title":{"en":"Ethanolamine Is a New Anti-Prion Compound","ja":"Ethanolamine Is a New Anti-Prion Compound"},"authors":{"en":[{"name":"Uchiyama Keiji"},{"name":"Hara Hideyuki"},{"name":"Chida Junji"},{"name":"Pasiana Agriani"},{"name":"Imamura Morikazu"},{"name":"Mori Tsuyoshi"},{"name":"Takatsuki Hanae"},{"name":"Atarashi Ryuichiro"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"内山 圭司"},{"name":"原 英之"},{"name":"千田 淳司"},{"name":"Pasiana Agriani"},{"name":"Imamura Morikazu"},{"name":"Mori Tsuyoshi"},{"name":"Takatsuki Hanae"},{"name":"Atarashi Ryuichiro"},{"name":"坂口 末廣"}]},"description":{"en":"Prion diseases are a group of fatal neurodegenerative disorders caused by accumulation of proteinaceous infectious particles, or prions, which mainly consist of the abnormally folded, amyloidogenic prion protein, designated PrP. PrP is produced through conformational conversion of the cellular isoform of prion protein, PrP, in the brain. To date, no effective therapies for prion diseases have been developed. In this study, we incidentally noticed that mouse neuroblastoma N2a cells persistently infected with 22L scrapie prions, termed N2aC24L1-3 cells, reduced PrP levels when cultured in advanced Dulbecco's modified eagle medium (DMEM) but not in classic DMEM. PrP levels remained unchanged in prion-uninfected parent N2aC24 cells cultured in advanced DMEM. These results suggest that advanced DMEM may contain an anti-prion compound(s). We then successfully identified ethanolamine in advanced DMEM has an anti-prion activity. Ethanolamine reduced PrP levels in N2aC24L1-3 cells, but not PrP levels in N2aC24 cells. Also, oral administration of ethanolamine through drinking water delayed prion disease in mice intracerebrally inoculated with RML scrapie prions. These results suggest that ethanolamine could be a new anti-prion compound.","ja":"Prion diseases are a group of fatal neurodegenerative disorders caused by accumulation of proteinaceous infectious particles, or prions, which mainly consist of the abnormally folded, amyloidogenic prion protein, designated PrP. PrP is produced through conformational conversion of the cellular isoform of prion protein, PrP, in the brain. To date, no effective therapies for prion diseases have been developed. In this study, we incidentally noticed that mouse neuroblastoma N2a cells persistently infected with 22L scrapie prions, termed N2aC24L1-3 cells, reduced PrP levels when cultured in advanced Dulbecco's modified eagle medium (DMEM) but not in classic DMEM. PrP levels remained unchanged in prion-uninfected parent N2aC24 cells cultured in advanced DMEM. These results suggest that advanced DMEM may contain an anti-prion compound(s). We then successfully identified ethanolamine in advanced DMEM has an anti-prion activity. Ethanolamine reduced PrP levels in N2aC24L1-3 cells, but not PrP levels in N2aC24 cells. Also, oral administration of ethanolamine through drinking water delayed prion disease in mice intracerebrally inoculated with RML scrapie prions. These results suggest that ethanolamine could be a new anti-prion compound."},"publication_date":"2021-10-29","publication_name":{"en":"International Journal of Molecular Sciences","ja":"International Journal of Molecular Sciences"},"volume":"Vol.22","number":"No.21","starting_page":"11742","ending_page":"11742","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3390/ijms222111742"],"issn":["1422-0067"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:5, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117718","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/33980968","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=388672","label":"url"}],"paper_title":{"en":"Neurotropic influenza A virus infection causes prion protein misfolding into infectious prions in neuroblastoma cells.","ja":"Neurotropic influenza A virus infection causes prion protein misfolding into infectious prions in neuroblastoma cells."},"authors":{"en":[{"name":"Hara Hideyuki"},{"name":"Chida Junji"},{"name":"Uchiyama Keiji"},{"name":"Pasiana Agriani Dini"},{"name":"Takahashi Etsuhisa"},{"name":"Kido Hiroshi"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"原 英之"},{"name":"千田 淳司"},{"name":"内山 圭司"},{"name":"Pasiana Agriani Dini"},{"name":"高橋 悦久"},{"name":"木戸 博"},{"name":"坂口 末廣"}]},"publication_date":"2021-05-12","publication_name":{"en":"Scientific Reports","ja":"Scientific Reports"},"volume":"Vol.11","number":"No.1","starting_page":"10109","ending_page":"10109","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/s41598-021-89586-6"],"issn":["2045-2322"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:6, {"insert":{"user_id":"5000035549","type":"published_papers","id":"32375916"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/116339","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/33806892","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85102845949&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=375320","label":"url"}],"paper_title":{"en":"Vaporized Hydrogen Peroxide and Ozone Gas Synergistically Reduce Prion Infectivity on Stainless Steel Wire.","ja":"Vaporized Hydrogen Peroxide and Ozone Gas Synergistically Reduce Prion Infectivity on Stainless Steel Wire."},"authors":{"en":[{"name":"Hara Hideyuki"},{"name":"Chida Junji"},{"name":"Pasiana Dini Agriani"},{"name":"Uchiyama Keiji"},{"name":"Kikuchi Yutaka"},{"name":"Naito Tomoko"},{"name":"Takahashi Yuichi"},{"name":"Yamamura Junji"},{"name":"Kuromatsu Hisashi"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"原 英之"},{"name":"千田 淳司"},{"name":"Pasiana Agriani Dini"},{"name":"内山 圭司"},{"name":"Kikuchi Yutaka"},{"name":"Naito Tomoko"},{"name":"Takahashi Yuichi"},{"name":"Yamamura Junji"},{"name":"Kuromatsu Hisashi"},{"name":"坂口 末廣"}]},"description":{"en":"Prions are infectious agents causing prion diseases, which include Creutzfeldt-Jakob disease (CJD) in humans. Several cases have been reported to be transmitted through medical instruments that were used for preclinical CJD patients, raising public health concerns on iatrogenic transmissions of the disease. Since preclinical CJD patients are currently difficult to identify, medical instruments need to be adequately sterilized so as not to transmit the disease. In this study, we investigated the sterilizing activity of two oxidizing agents, ozone gas and vaporized hydrogen peroxide, against prions fixed on stainless steel wires using a mouse bioassay. Mice intracerebrally implanted with prion-contaminated stainless steel wires treated with ozone gas or vaporized hydrogen peroxide developed prion disease later than those implanted with control prion-contaminated stainless steel wires, indicating that ozone gas and vaporized hydrogen peroxide could reduce prion infectivity on wires. Incubation times were further elongated in mice implanted with prion-contaminated stainless steel wires treated with ozone gas-mixed vaporized hydrogen peroxide, indicating that ozone gas mixed with vaporized hydrogen peroxide reduces prions on these wires more potently than ozone gas or vaporized hydrogen peroxide. These results suggest that ozone gas mixed with vaporized hydrogen peroxide might be more useful for prion sterilization than ozone gas or vaporized hydrogen peroxide alone.","ja":"Prions are infectious agents causing prion diseases, which include Creutzfeldt-Jakob disease (CJD) in humans. Several cases have been reported to be transmitted through medical instruments that were used for preclinical CJD patients, raising public health concerns on iatrogenic transmissions of the disease. Since preclinical CJD patients are currently difficult to identify, medical instruments need to be adequately sterilized so as not to transmit the disease. In this study, we investigated the sterilizing activity of two oxidizing agents, ozone gas and vaporized hydrogen peroxide, against prions fixed on stainless steel wires using a mouse bioassay. Mice intracerebrally implanted with prion-contaminated stainless steel wires treated with ozone gas or vaporized hydrogen peroxide developed prion disease later than those implanted with control prion-contaminated stainless steel wires, indicating that ozone gas and vaporized hydrogen peroxide could reduce prion infectivity on wires. Incubation times were further elongated in mice implanted with prion-contaminated stainless steel wires treated with ozone gas-mixed vaporized hydrogen peroxide, indicating that ozone gas mixed with vaporized hydrogen peroxide reduces prions on these wires more potently than ozone gas or vaporized hydrogen peroxide. These results suggest that ozone gas mixed with vaporized hydrogen peroxide might be more useful for prion sterilization than ozone gas or vaporized hydrogen peroxide alone."},"publication_date":"2021-03-23","publication_name":{"en":"International Journal of Molecular Sciences","ja":"International Journal of Molecular Sciences"},"volume":"Vol.22","number":"No.6","starting_page":"3268","ending_page":"3268","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3390/ijms22063268"],"issn":["1422-0067"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:7, {"insert":{"user_id":"5000035549","type":"published_papers","id":"30800935"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/115634","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/33019549","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85091919621&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=372280","label":"url"}],"paper_title":{"en":"Strain-Dependent Prion Infection in Mice Expressing Prion Protein with Deletion of Central Residues 91-106.","ja":"Strain-Dependent Prion Infection in Mice Expressing Prion Protein with Deletion of Central Residues 91-106."},"authors":{"en":[{"name":"Uchiyama Keiji"},{"name":"Hironori Miyata"},{"name":"Yoshitaka Yamaguchi"},{"name":"Morikazu Imamura"},{"name":"Mariya Okazaki"},{"name":"Agriani Dini Pasiana"},{"name":"Chida Junji"},{"name":"Hara Hideyuki"},{"name":"Ryuichiro Atarashi"},{"name":"Hitomi Watanabe"},{"name":"Gen Kondoh"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"内山 圭司"},{"name":"Hironori Miyata"},{"name":"Yoshitaka Yamaguchi"},{"name":"Morikazu Imamura"},{"name":"岡崎 摩利矢"},{"name":"Pasiana Agriani Dini"},{"name":"千田 淳司"},{"name":"原 英之"},{"name":"Ryuichiro Atarashi"},{"name":"Hitomi Watanabe"},{"name":"Gen Kondoh"},{"name":"坂口 末廣"}]},"description":{"en":"Conformational conversion of the cellular prion protein, PrP, into the abnormally folded isoform, PrP, is a key pathogenic event in prion diseases. However, the exact conversion mechanism remains largely unknown. Transgenic mice expressing PrP with a deletion of the central residues 91-106 were generated in the absence of endogenous PrP, designated Tg(PrP∆91-106)/ mice and intracerebrally inoculated with various prions. Tg(PrP∆91-106)/ mice were resistant to RML, 22L and FK-1 prions, neither producing PrP∆91-106 or prions in the brain nor developing disease after inoculation. However, they remained marginally susceptible to bovine spongiform encephalopathy (BSE) prions, developing disease after elongated incubation times and accumulating PrP∆91-106 and prions in the brain after inoculation with BSE prions. Recombinant PrP∆91-104 converted into PrP∆91-104 after incubation with BSE-PrP-prions but not with RML- and 22L-PrP-prions, in a protein misfolding cyclic amplification assay. However, digitonin and heparin stimulated the conversion of PrP∆91-104 into PrP∆91-104 even after incubation with RML- and 22L-PrP-prions. These results suggest that residues 91-106 or 91-104 of PrP are crucially involved in prion pathogenesis in a strain-dependent manner and may play a similar role to digitonin and heparin in the conversion of PrP into PrP.","ja":"Conformational conversion of the cellular prion protein, PrP, into the abnormally folded isoform, PrP, is a key pathogenic event in prion diseases. However, the exact conversion mechanism remains largely unknown. Transgenic mice expressing PrP with a deletion of the central residues 91-106 were generated in the absence of endogenous PrP, designated Tg(PrP∆91-106)/ mice and intracerebrally inoculated with various prions. Tg(PrP∆91-106)/ mice were resistant to RML, 22L and FK-1 prions, neither producing PrP∆91-106 or prions in the brain nor developing disease after inoculation. However, they remained marginally susceptible to bovine spongiform encephalopathy (BSE) prions, developing disease after elongated incubation times and accumulating PrP∆91-106 and prions in the brain after inoculation with BSE prions. Recombinant PrP∆91-104 converted into PrP∆91-104 after incubation with BSE-PrP-prions but not with RML- and 22L-PrP-prions, in a protein misfolding cyclic amplification assay. However, digitonin and heparin stimulated the conversion of PrP∆91-104 into PrP∆91-104 even after incubation with RML- and 22L-PrP-prions. These results suggest that residues 91-106 or 91-104 of PrP are crucially involved in prion pathogenesis in a strain-dependent manner and may play a similar role to digitonin and heparin in the conversion of PrP into PrP."},"publication_date":"2020-10-01","publication_name":{"en":"International Journal of Molecular Sciences","ja":"International Journal of Molecular Sciences"},"volume":"Vol.21","number":"No.19","starting_page":"7260","ending_page":"7260","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3390/ijms21197260"],"issn":["1422-0067"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:8, {"insert":{"user_id":"5000035549","type":"published_papers","id":"30778828"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/115618","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/32985542","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85091653225&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=372281","label":"url"}],"paper_title":{"en":"Impairment of cerebellar long-term depression and GABAergic transmission in prion protein deficient mice ectopically expressing PrPLP/Dpl.","ja":"Impairment of cerebellar long-term depression and GABAergic transmission in prion protein deficient mice ectopically expressing PrPLP/Dpl."},"authors":{"en":[{"name":"Yasushi Kishimoto"},{"name":"Moritoshi Hirono"},{"name":"Ryuichiro Atarashi"},{"name":"Sakaguchi Suehiro"},{"name":"Tohru Yoshioka"},{"name":"Shigeru Katamine"},{"name":"Yutaka Kirino"}],"ja":[{"name":"Yasushi Kishimoto"},{"name":"Moritoshi Hirono"},{"name":"Ryuichiro Atarashi"},{"name":"坂口 末廣"},{"name":"Tohru Yoshioka"},{"name":"Shigeru Katamine"},{"name":"Yutaka Kirino"}]},"publication_date":"2020-09-28","publication_name":{"en":"Scientific Reports","ja":"Scientific Reports"},"volume":"Vol.10","number":"No.1","starting_page":"15900","ending_page":"15900","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/s41598-020-72753-6"],"issn":["2045-2322"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:9, {"insert":{"user_id":"5000035549","type":"published_papers","id":"30800936"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/115633","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/32872280","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85090181761&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=372282","label":"url"}],"paper_title":{"en":"N-terminal Regions of Prion Protein: Functions and Roles in Prion Diseases.","ja":"N-terminal Regions of Prion Protein: Functions and Roles in Prion Diseases."},"authors":{"en":[{"name":"Hara Hideyuki"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"原 英之"},{"name":"坂口 末廣"}]},"description":{"en":"The normal cellular isoform of prion protein, designated PrP, is constitutively converted to the abnormally folded, amyloidogenic isoform, PrP, in prion diseases, which include Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals. PrP is a membrane glycoprotein consisting of the non-structural -terminal domain and the globular C-terminal domain. During conversion of PrP to PrP, its 2/3 C-terminal region undergoes marked structural changes, forming a protease-resistant structure. In contrast, the N-terminal region remains protease-sensitive in PrP. Reverse genetic studies using reconstituted PrP-knockout mice with various mutant PrP molecules have revealed that the N-terminal domain has an important role in the normal function of PrP and the conversion of PrP to PrP. The N-terminal domain includes various characteristic regions, such as the positively charged residue-rich polybasic region, the octapeptide repeat (OR) region consisting of five repeats of an octapeptide sequence, and the post-OR region with another positively charged residue-rich polybasic region followed by a stretch of hydrophobic residues. We discuss the normal functions of PrP, the conversion of PrP to PrP, and the neurotoxicity of PrP by focusing on the roles of the N-terminal regions in these topics.","ja":"The normal cellular isoform of prion protein, designated PrP, is constitutively converted to the abnormally folded, amyloidogenic isoform, PrP, in prion diseases, which include Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals. PrP is a membrane glycoprotein consisting of the non-structural -terminal domain and the globular C-terminal domain. During conversion of PrP to PrP, its 2/3 C-terminal region undergoes marked structural changes, forming a protease-resistant structure. In contrast, the N-terminal region remains protease-sensitive in PrP. Reverse genetic studies using reconstituted PrP-knockout mice with various mutant PrP molecules have revealed that the N-terminal domain has an important role in the normal function of PrP and the conversion of PrP to PrP. The N-terminal domain includes various characteristic regions, such as the positively charged residue-rich polybasic region, the octapeptide repeat (OR) region consisting of five repeats of an octapeptide sequence, and the post-OR region with another positively charged residue-rich polybasic region followed by a stretch of hydrophobic residues. We discuss the normal functions of PrP, the conversion of PrP to PrP, and the neurotoxicity of PrP by focusing on the roles of the N-terminal regions in these topics."},"publication_date":"2020-08-28","publication_name":{"en":"International Journal of Molecular Sciences","ja":"International Journal of Molecular Sciences"},"volume":"Vol.21","number":"No.17","starting_page":"E6233","ending_page":"E6233","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3390/ijms21176233"],"issn":["1422-0067"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:10, {"insert":{"user_id":"5000035549","type":"published_papers","id":"30377474"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/115613","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/32845931","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=371058","label":"url"}],"paper_title":{"en":"Prion protein signaling induces M2 macrophage polarization and protects from lethal influenza infection in mice.","ja":"Prion protein signaling induces M2 macrophage polarization and protects from lethal influenza infection in mice."},"authors":{"en":[{"name":"Chida Junji"},{"name":"Hara Hideyuki"},{"name":"Uchiyama Keiji"},{"name":"Takahashi Etsuhisa"},{"name":"Miyata Hironori"},{"name":"Kosako Hidetaka"},{"name":"Tomioka Yukiko"},{"name":"Ito Toshihiro"},{"name":"Horiuchi Hiroyuki"},{"name":"Matsuda Haruo"},{"name":"Kido Hiroshi"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"千田 淳司"},{"name":"原 英之"},{"name":"内山 圭司"},{"name":"高橋 悦久"},{"name":"Miyata Hironori"},{"name":"小迫 英尊"},{"name":"Tomioka Yukiko"},{"name":"Ito Toshihiro"},{"name":"Horiuchi Hiroyuki"},{"name":"Matsuda Haruo"},{"name":"木戸 博"},{"name":"坂口 末廣"}]},"description":{"en":"The cellular prion protein, PrPC, is a glycosylphosphatidylinositol anchored-membrane glycoprotein expressed most abundantly in neuronal and to a lesser extent in non-neuronal cells. Its conformational conversion into the amyloidogenic isoform in neurons is a key pathogenic event in prion diseases, including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals. However, the normal functions of PrPC remain largely unknown, particularly in non-neuronal cells. Here we show that stimulation of PrPC with anti-PrP monoclonal antibodies (mAbs) protected mice from lethal infection with influenza A viruses (IAVs), with abundant accumulation of anti-inflammatory M2 macrophages with activated Src family kinases (SFKs) in infected lungs. A SFK inhibitor dasatinib inhibited M2 macrophage accumulation in IAV-infected lungs after treatment with anti-PrP mAbs and abolished the anti-PrP mAb-induced protective activity against lethal influenza infection in mice. We also show that stimulation of PrPC with anti-PrP mAbs induced M2 polarization in peritoneal macrophages through SFK activation in vitro and in vivo. These results indicate that PrPC could activate SFK in macrophages and induce macrophage polarization to an anti-inflammatory M2 phenotype after stimulation with anti-PrP mAbs, thereby eliciting protective activity against lethal infection with IAVs in mice after treatment with anti-PrP mAbs. These results also highlight PrPC as a novel therapeutic target for IAV infection.","ja":"The cellular prion protein, PrPC, is a glycosylphosphatidylinositol anchored-membrane glycoprotein expressed most abundantly in neuronal and to a lesser extent in non-neuronal cells. Its conformational conversion into the amyloidogenic isoform in neurons is a key pathogenic event in prion diseases, including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals. However, the normal functions of PrPC remain largely unknown, particularly in non-neuronal cells. Here we show that stimulation of PrPC with anti-PrP monoclonal antibodies (mAbs) protected mice from lethal infection with influenza A viruses (IAVs), with abundant accumulation of anti-inflammatory M2 macrophages with activated Src family kinases (SFKs) in infected lungs. A SFK inhibitor dasatinib inhibited M2 macrophage accumulation in IAV-infected lungs after treatment with anti-PrP mAbs and abolished the anti-PrP mAb-induced protective activity against lethal influenza infection in mice. We also show that stimulation of PrPC with anti-PrP mAbs induced M2 polarization in peritoneal macrophages through SFK activation in vitro and in vivo. These results indicate that PrPC could activate SFK in macrophages and induce macrophage polarization to an anti-inflammatory M2 phenotype after stimulation with anti-PrP mAbs, thereby eliciting protective activity against lethal infection with IAVs in mice after treatment with anti-PrP mAbs. These results also highlight PrPC as a novel therapeutic target for IAV infection."},"publication_date":"2020-08-26","publication_name":{"en":"PLoS Pathogens","ja":"PLoS Pathogens"},"volume":"Vol.16","number":"No.8","starting_page":"e1008823","ending_page":"e1008823","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1371/journal.ppat.1008823"],"issn":["1553-7374"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:11, {"insert":{"user_id":"5000035549","type":"published_papers","id":"30778830"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/115747","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/31814573","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85078510915&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=372283","label":"url"}],"paper_title":{"en":"Prion Protein Is a Novel Modulator of Influenza: Its Potential Implications for Anti-Influenza Therapeutics.","ja":"Prion Protein Is a Novel Modulator of Influenza: Its Potential Implications for Anti-Influenza Therapeutics."},"authors":{"en":[{"name":"Sakaguchi Suehiro"},{"name":"Chida Junji"}],"ja":[{"name":"坂口 末廣"},{"name":"千田 淳司"}]},"publication_date":"2019-12-09","publication_name":{"en":"Current Issues in Molecular Biology","ja":"Current Issues in Molecular Biology"},"volume":"Vol.37","starting_page":"21","ending_page":"32","languages":["eng"],"referee":true,"identifiers":{"doi":["10.21775/cimb.037.021"],"issn":["1467-3045"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:12, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/31707632","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85074844020&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=368662","label":"url"}],"paper_title":{"en":"The N-Terminal Polybasic Region of Prion Protein Is Crucial in Prion Pathogenesis Independently of the Octapeptide Repeat Region","ja":"The N-Terminal Polybasic Region of Prion Protein Is Crucial in Prion Pathogenesis Independently of the Octapeptide Repeat Region"},"authors":{"en":[{"name":"Das Rani Nandita"},{"name":"Miyata Hironori"},{"name":"Hara Hideyuki"},{"name":"Chida Junji"},{"name":"Uchiyama Keiji"},{"name":"Masujin Kentaro"},{"name":"Watanabe Hitomi"},{"name":"Kondoh Gen"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"Das Rani Nandita"},{"name":"Miyata Hironori"},{"name":"原 英之"},{"name":"千田 淳司"},{"name":"内山 圭司"},{"name":"Masujin Kentaro"},{"name":"Watanabe Hitomi"},{"name":"Kondoh Gen"},{"name":"坂口 末廣"}]},"description":{"en":"Conformational conversion of the cellular isoform of prion protein, designated PrP, into the abnormally folded, amyloidogenic isoform, PrP, is an essential pathogenic event in prion diseases. However, the exact conversion mechanism remains largely unknown. Lines of evidence indicate that the N-terminal domain, which includes the N-terminal, positively charged polybasic region and the octapeptide repeat (OR) region, is important for PrP to convert into PrP after infection with prions. To further gain insights into the role of the polybasic region and the OR region in prion pathogenesis, we generated two different transgenic mice, designated Tg(PrP3K3A)/Prnp and Tg(PrP3K3A∆OR)/Prnp mice, which express PrP with lysine residues at codons 23, 24, and 27 in the polybasic region mutated with or without a deletion of the OR region on the Prnp background, respectively, and intracerebrally inoculated them with RML and 22L prions. We show that Tg(PrP3K3A)/Prnp mice were highly resistant to the prions, indicating that lysine residues at 23, 24, and 27 could be important for the polybasic region to support prion infection. Tg(PrP3K3A∆OR)/Prnp mice also had reduced susceptibility to RML and 22L prions equivalent to Tg(PrP3K3A)/Prnp mice. The pre-OR region, including the polybasic region, of PrP3K3A∆OR, but not PrP3K3A, was unusually converted to a protease-resistant structure during conversion to PrP3K3A∆OR. These results suggest that, while the OR region could affect the conformation of the polybasic region during conversion of PrP into PrP, the polybasic region could play a crucial role in prion pathogenesis independently of the OR region.","ja":"Conformational conversion of the cellular isoform of prion protein, designated PrP, into the abnormally folded, amyloidogenic isoform, PrP, is an essential pathogenic event in prion diseases. However, the exact conversion mechanism remains largely unknown. Lines of evidence indicate that the N-terminal domain, which includes the N-terminal, positively charged polybasic region and the octapeptide repeat (OR) region, is important for PrP to convert into PrP after infection with prions. To further gain insights into the role of the polybasic region and the OR region in prion pathogenesis, we generated two different transgenic mice, designated Tg(PrP3K3A)/Prnp and Tg(PrP3K3A∆OR)/Prnp mice, which express PrP with lysine residues at codons 23, 24, and 27 in the polybasic region mutated with or without a deletion of the OR region on the Prnp background, respectively, and intracerebrally inoculated them with RML and 22L prions. We show that Tg(PrP3K3A)/Prnp mice were highly resistant to the prions, indicating that lysine residues at 23, 24, and 27 could be important for the polybasic region to support prion infection. Tg(PrP3K3A∆OR)/Prnp mice also had reduced susceptibility to RML and 22L prions equivalent to Tg(PrP3K3A)/Prnp mice. The pre-OR region, including the polybasic region, of PrP3K3A∆OR, but not PrP3K3A, was unusually converted to a protease-resistant structure during conversion to PrP3K3A∆OR. These results suggest that, while the OR region could affect the conformation of the polybasic region during conversion of PrP into PrP, the polybasic region could play a crucial role in prion pathogenesis independently of the OR region."},"publication_date":"2019-11-09","publication_name":{"en":"Molecular Neurobiology","ja":"Molecular Neurobiology"},"volume":"Vol.57","starting_page":"1203","ending_page":"1216","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s12035-019-01804-5"],"issn":["1559-1182"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:13, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/112207","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/30222366","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=356502","label":"url"}],"paper_title":{"en":"Roles of Prion Protein in Virus Infections.","ja":"Roles of Prion Protein in Virus Infections."},"authors":{"en":[{"name":"Sakaguchi Suehiro"},{"name":"Chida Junji"}],"ja":[{"name":"坂口 末廣"},{"name":"千田 淳司"}]},"description":{"en":"The normal cellular prion protein, designated PrP, is a membrane glycoprotein expressed most abundantly in brains, particularly by neurons, and to a lesser extent in non-neuronal tissues including lungs. Conformational conversion of PrP into the amyloidogenic isoform is a key pathogenic event in prion diseases. We recently found that PrP has a protective role against infection with influenza A viruses (IAVs) in mice by reducing reactive oxygen species in the lungs after infection with IAVs. The antioxidative activity of PrP is probably attributable to its function to activate antioxidative enzyme Cu/Zn-superoxide dismutase, or SOD1, through regulating Cu content in lungs infected with IAVs. Oxidative stress could play a pivotal role in the pathogenesis of a wide range of viral infections. Here, we introduce our and others' studies on the role of PrP in viral infections, and raise the attractive possibility that PrP might be a novel target molecule for development of antioxidative therapeutics against not only IAV infection but also other viral infections.","ja":"The normal cellular prion protein, designated PrP, is a membrane glycoprotein expressed most abundantly in brains, particularly by neurons, and to a lesser extent in non-neuronal tissues including lungs. Conformational conversion of PrP into the amyloidogenic isoform is a key pathogenic event in prion diseases. We recently found that PrP has a protective role against infection with influenza A viruses (IAVs) in mice by reducing reactive oxygen species in the lungs after infection with IAVs. The antioxidative activity of PrP is probably attributable to its function to activate antioxidative enzyme Cu/Zn-superoxide dismutase, or SOD1, through regulating Cu content in lungs infected with IAVs. Oxidative stress could play a pivotal role in the pathogenesis of a wide range of viral infections. Here, we introduce our and others' studies on the role of PrP in viral infections, and raise the attractive possibility that PrP might be a novel target molecule for development of antioxidative therapeutics against not only IAV infection but also other viral infections."},"publication_date":"2018-10","publication_name":{"en":"DNA and Cell Biology","ja":"DNA and Cell Biology"},"volume":"Vol.37","number":"No.10","starting_page":"808","ending_page":"811","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1089/dna.2018.4402"],"issn":["1557-7430"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:14, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/112206","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/29723291","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=342964","label":"url"}],"paper_title":{"en":"Prion protein protects mice from lethal infection with influenza A viruses.","ja":"Prion protein protects mice from lethal infection with influenza A viruses."},"authors":{"en":[{"name":"Chida Junji"},{"name":"Hara Hideyuki"},{"name":"Yano Masashi"},{"name":"Uchiyama Keiji"},{"name":"Das Nandita Rani"},{"name":"Takahashi Etsuhisa"},{"name":"Miyata Hironori"},{"name":"Tomioka Yukiko"},{"name":"Ito Toshihiro"},{"name":"Kido Hiroshi"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"千田 淳司"},{"name":"原 英之"},{"name":"矢野 雅司"},{"name":"内山 圭司"},{"name":"Nandita Rani Das"},{"name":"高橋 悦久"},{"name":"Miyata Hironori"},{"name":"富岡 有紀子"},{"name":"Ito Toshihiro"},{"name":"木戸 博"},{"name":"坂口 末廣"}]},"description":{"en":"The cellular prion protein, designated PrPC, is a membrane glycoprotein expressed abundantly in brains and to a lesser extent in other tissues. Conformational conversion of PrPC into the amyloidogenic isoform is a key pathogenic event in prion diseases. However, the physiological functions of PrPC remain largely unknown, particularly in non-neuronal tissues. Here, we show that PrPC is expressed in lung epithelial cells, including alveolar type 1 and 2 cells and bronchiolar Clara cells. Compared with wild-type (WT) mice, PrPC-null mice (Prnp0/0) were highly susceptible to influenza A viruses (IAVs), with higher mortality. Infected Prnp0/0 lungs were severely injured, with higher inflammation and higher apoptosis of epithelial cells, and contained higher reactive oxygen species (ROS) than control WT lungs. Treatment with a ROS scavenger or an inhibitor of xanthine oxidase (XO), a major ROS-generating enzyme in IAV-infected lungs, rescued Prnp0/0 mice from the lethal infection with IAV. Moreover, Prnp0/0 mice transgenic for PrP with a deletion of the Cu-binding octapeptide repeat (OR) region, Tg(PrPOR)/Prnp0/0 mice, were also highly susceptible to IAV infection. These results indicate that PrPC has a protective role against lethal infection with IAVs through the Cu-binding OR region by reducing ROS in infected lungs. Cu content and the activity of anti-oxidant enzyme Cu/Zn-dependent superoxide dismutase, SOD1, were lower in Prnp0/0 and Tg(PrPOR)/Prnp0/0 lungs than in WT lungs. It is thus conceivable that PrPC functions to maintain Cu content and regulate SOD1 through the OR region in lungs, thereby reducing ROS in IAV-infected lungs and eventually protecting them from lethal infection with IAVs. Our current results highlight the role of PrPC in protection against IAV infection, and suggest that PrPC might be a novel target molecule for anti-influenza therapeutics.","ja":"The cellular prion protein, designated PrPC, is a membrane glycoprotein expressed abundantly in brains and to a lesser extent in other tissues. Conformational conversion of PrPC into the amyloidogenic isoform is a key pathogenic event in prion diseases. However, the physiological functions of PrPC remain largely unknown, particularly in non-neuronal tissues. Here, we show that PrPC is expressed in lung epithelial cells, including alveolar type 1 and 2 cells and bronchiolar Clara cells. Compared with wild-type (WT) mice, PrPC-null mice (Prnp0/0) were highly susceptible to influenza A viruses (IAVs), with higher mortality. Infected Prnp0/0 lungs were severely injured, with higher inflammation and higher apoptosis of epithelial cells, and contained higher reactive oxygen species (ROS) than control WT lungs. Treatment with a ROS scavenger or an inhibitor of xanthine oxidase (XO), a major ROS-generating enzyme in IAV-infected lungs, rescued Prnp0/0 mice from the lethal infection with IAV. Moreover, Prnp0/0 mice transgenic for PrP with a deletion of the Cu-binding octapeptide repeat (OR) region, Tg(PrPOR)/Prnp0/0 mice, were also highly susceptible to IAV infection. These results indicate that PrPC has a protective role against lethal infection with IAVs through the Cu-binding OR region by reducing ROS in infected lungs. Cu content and the activity of anti-oxidant enzyme Cu/Zn-dependent superoxide dismutase, SOD1, were lower in Prnp0/0 and Tg(PrPOR)/Prnp0/0 lungs than in WT lungs. It is thus conceivable that PrPC functions to maintain Cu content and regulate SOD1 through the OR region in lungs, thereby reducing ROS in IAV-infected lungs and eventually protecting them from lethal infection with IAVs. Our current results highlight the role of PrPC in protection against IAV infection, and suggest that PrPC might be a novel target molecule for anti-influenza therapeutics."},"publication_date":"2018-05-03","publication_name":{"en":"PLoS Pathogens","ja":"PLoS Pathogens"},"volume":"Vol.14","number":"No.5","starting_page":"e1007049","ending_page":"e1007049","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1371/journal.ppat.1007049"],"issn":["1553-7374"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:15, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/114545","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/29625583","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85044987648&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=338399","label":"url"}],"paper_title":{"en":"Structural and mechanistic aspects influencing the ADAM10-mediated shedding of the prion protein.","ja":"Structural and mechanistic aspects influencing the ADAM10-mediated shedding of the prion protein."},"authors":{"en":[{"name":"Linsenmeier Luise"},{"name":"Mohammadi Behnam"},{"name":"Wetzel Sebastian"},{"name":"Puig Berta"},{"name":"Jackson S. Walker"},{"name":"Hartmann Alexander"},{"name":"Uchiyama Keiji"},{"name":"Sakaguchi Suehiro"},{"name":"Endres Kristina"},{"name":"Tatzelt Jörg"},{"name":"Saftig Paul"},{"name":"Glatzel Markus"},{"name":"Altmeppen C. Hermann"}],"ja":[{"name":"Linsenmeier Luise"},{"name":"Mohammadi Behnam"},{"name":"Wetzel Sebastian"},{"name":"Puig Berta"},{"name":"Jackson S. Walker"},{"name":"Hartmann Alexander"},{"name":"内山 圭司"},{"name":"坂口 末廣"},{"name":"Endres Kristina"},{"name":"Tatzelt Jörg"},{"name":"Saftig Paul"},{"name":"Glatzel Markus"},{"name":"Altmeppen C. Hermann"}]},"description":{"en":"Proteolytic processing of the prion protein (PrP<superscript>C</superscript>) by endogenous proteases generates bioactive membrane-bound and soluble fragments which may help to explain the pleiotropic roles of this protein in the nervous system and in brain diseases. Shedding of almost full-length PrP<superscript>C</superscript> into the extracellular space by the metalloprotease ADAM10 is of peculiar relevance since soluble PrP stimulates axonal outgrowth and is protective in neurodegenerative conditions such as Alzheimer's and prion disease. However, molecular determinates and mechanisms regulating the shedding of PrP are entirely unknown. We produced an antibody recognizing the neo-epitope of shed PrP generated by ADAM10 in biological samples and used it to study structural and mechanistic aspects affecting the shedding. For this, we investigated genetically modified cellular and murine models by biochemical and morphological approaches. We show that the novel antibody specifically detects shed PrP in cell culture supernatants and murine brain. We demonstrate that ADAM10 is the exclusive sheddase of PrP<superscript>C</superscript> in the nervous system and reveal that the glycosylation state and type of membrane-anchorage of PrP<superscript>C</superscript> severely affect its shedding. Furthermore, we provide evidence that PrP shedding can be modulated by pharmacological inhibition and stimulation and present data suggesting that shedding is a relevant part of a compensatory network ensuring PrP<superscript>C</superscript> homeostasis of the cell. With the new antibody, our study introduces a new tool to reliably investigate PrP-shedding. In addition, this study provides novel and important insight into the regulation of this cleavage event, which is likely to be relevant for diagnostic and therapeutic approaches even beyond neurodegeneration.","ja":"Proteolytic processing of the prion protein (PrP<superscript>C</superscript>) by endogenous proteases generates bioactive membrane-bound and soluble fragments which may help to explain the pleiotropic roles of this protein in the nervous system and in brain diseases. Shedding of almost full-length PrP<superscript>C</superscript> into the extracellular space by the metalloprotease ADAM10 is of peculiar relevance since soluble PrP stimulates axonal outgrowth and is protective in neurodegenerative conditions such as Alzheimer's and prion disease. However, molecular determinates and mechanisms regulating the shedding of PrP are entirely unknown. We produced an antibody recognizing the neo-epitope of shed PrP generated by ADAM10 in biological samples and used it to study structural and mechanistic aspects affecting the shedding. For this, we investigated genetically modified cellular and murine models by biochemical and morphological approaches. We show that the novel antibody specifically detects shed PrP in cell culture supernatants and murine brain. We demonstrate that ADAM10 is the exclusive sheddase of PrP<superscript>C</superscript> in the nervous system and reveal that the glycosylation state and type of membrane-anchorage of PrP<superscript>C</superscript> severely affect its shedding. Furthermore, we provide evidence that PrP shedding can be modulated by pharmacological inhibition and stimulation and present data suggesting that shedding is a relevant part of a compensatory network ensuring PrP<superscript>C</superscript> homeostasis of the cell. With the new antibody, our study introduces a new tool to reliably investigate PrP-shedding. In addition, this study provides novel and important insight into the regulation of this cleavage event, which is likely to be relevant for diagnostic and therapeutic approaches even beyond neurodegeneration."},"publication_date":"2018-04-06","publication_name":{"en":"Molecular Neurodegeneration","ja":"Molecular Neurodegeneration"},"volume":"Vol.13","number":"No.1","starting_page":"18","ending_page":"18","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1186/s13024-018-0248-6"],"issn":["1750-1326"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:16, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/113067","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=356504","label":"url"}],"paper_title":{"en":"Cellular prion protein-mediated protection against influenza A virus infection.","ja":"Cellular prion protein-mediated protection against influenza A virus infection."},"authors":{"en":[{"name":"Chida Junji"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"千田 淳司"},{"name":"坂口 末廣"}]},"publication_date":"2018","publication_name":{"en":"Future Virology","ja":"Future Virology"},"volume":"Vol.14","number":"No.1","starting_page":"31","ending_page":"37","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2217/fvl-2018-0146"],"issn":["1746-0794"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:17, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/111465","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/29046443","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1050845762396495104/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=337787","label":"url"}],"paper_title":{"en":"Prion Protein Devoid of the Octapeptide Repeat Region Delays BSE Pathogenesis in Mice.","ja":"Prion Protein Devoid of the Octapeptide Repeat Region Delays BSE Pathogenesis in Mice."},"authors":{"en":[{"name":"Hara Hideyuki"},{"name":"Hironori Miyata"},{"name":"Nandita Rani Das"},{"name":"Chida Junji"},{"name":"Tatenobu Yoshimochi"},{"name":"Uchiyama Keiji"},{"name":"Hitomi Watanabe"},{"name":"Gen Kondoh"},{"name":"Takashi Yokoyama"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"原 英之"},{"name":"Hironori Miyata"},{"name":"Nandita Rani Das"},{"name":"千田 淳司"},{"name":"吉持 盾信"},{"name":"内山 圭司"},{"name":"Hitomi Watanabe"},{"name":"Gen Kondoh"},{"name":"Takashi Yokoyama"},{"name":"坂口 末廣"}]},"description":{"en":"Conformational conversion of the cellular isoform of prion protein, PrP, into the abnormally folded, amyloidogenic isoform, PrP, is a key pathogenic event in prion diseases, including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy (BSE) in animals. We previously reported that the octapeptide repeat (OR) region could be dispensable for converting PrP into PrP after infection with RML prions. We demonstrated that mice transgenically expressing mouse PrP with deletion of the OR region on the PrP knockout background, designated Tg(PrPΔOR)/ mice, did not show reduced susceptibility to RML scrapie prions, with abundant accumulation of PrPΔOR in their brains. We show here that Tg(PrPΔOR)/ mice were highly resistant to BSE prions, developing the disease with markedly elongated incubation times after infection with BSE prions. The conversion of PrPΔOR into PrPΔOR was markedly delayed in their brains. These results suggest that the OR region may have a crucial role in the conversion of PrP into PrP after infection with BSE prions. However, Tg(PrPΔOR)/ mice remained susceptible to RML and 22L scrapie prions, developing the disease without elongated incubation times after infection with RML and 22L prions. PrPΔOR accumulated only slightly less in the brains of RML- or 22L-infected Tg(PrPΔOR)/ mice than PrP in control wild-type mice. Taken together, these results indicate that the OR region of PrP could play a differential role in the pathogenesis of BSE prions and RML or 22L scrapie prions. Structure-function relationship studies of PrP conformational conversion into PrP are worthwhile to understand the mechanism of the conversion of PrP into PrP We show here that, by inoculating Tg(PrPΔOR)/ mice with the three different strains of RML, 22L, and BSE prions, the OR region could play a differential role in the conversion of PrP into PrP after infection with RML or 22L scrapie prions and BSE prions. PrPΔOR was efficiently converted into PrPΔOR after infection with RML and 22L prions. However, the conversion of PrPΔOR into PrPΔOR was markedly delayed after infection with BSE prions. Further investigation into the role of the OR region in the conversion of PrP into PrP after infection with BSE prions might be helpful for understanding the pathogenesis of BSE prions.","ja":"Conformational conversion of the cellular isoform of prion protein, PrP, into the abnormally folded, amyloidogenic isoform, PrP, is a key pathogenic event in prion diseases, including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy (BSE) in animals. We previously reported that the octapeptide repeat (OR) region could be dispensable for converting PrP into PrP after infection with RML prions. We demonstrated that mice transgenically expressing mouse PrP with deletion of the OR region on the PrP knockout background, designated Tg(PrPΔOR)/ mice, did not show reduced susceptibility to RML scrapie prions, with abundant accumulation of PrPΔOR in their brains. We show here that Tg(PrPΔOR)/ mice were highly resistant to BSE prions, developing the disease with markedly elongated incubation times after infection with BSE prions. The conversion of PrPΔOR into PrPΔOR was markedly delayed in their brains. These results suggest that the OR region may have a crucial role in the conversion of PrP into PrP after infection with BSE prions. However, Tg(PrPΔOR)/ mice remained susceptible to RML and 22L scrapie prions, developing the disease without elongated incubation times after infection with RML and 22L prions. PrPΔOR accumulated only slightly less in the brains of RML- or 22L-infected Tg(PrPΔOR)/ mice than PrP in control wild-type mice. Taken together, these results indicate that the OR region of PrP could play a differential role in the pathogenesis of BSE prions and RML or 22L scrapie prions. Structure-function relationship studies of PrP conformational conversion into PrP are worthwhile to understand the mechanism of the conversion of PrP into PrP We show here that, by inoculating Tg(PrPΔOR)/ mice with the three different strains of RML, 22L, and BSE prions, the OR region could play a differential role in the conversion of PrP into PrP after infection with RML or 22L scrapie prions and BSE prions. PrPΔOR was efficiently converted into PrPΔOR after infection with RML and 22L prions. However, the conversion of PrPΔOR into PrPΔOR was markedly delayed after infection with BSE prions. Further investigation into the role of the OR region in the conversion of PrP into PrP after infection with BSE prions might be helpful for understanding the pathogenesis of BSE prions."},"publication_date":"2018","publication_name":{"en":"Journal of Virology","ja":"Journal of Virology"},"volume":"Vol.92","number":"No.1","starting_page":"pii:e01368-17","ending_page":"pii:e01368-17","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1128/JVI.01368-17"],"issn":["1098-5514"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:18, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/112200","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/29099278","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85034055921&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=337786","label":"url"}],"paper_title":{"en":"Novel Amplification Mechanism of Prions through Disrupting Sortilin-Mediated Trafficking.","ja":"Novel Amplification Mechanism of Prions through Disrupting Sortilin-Mediated Trafficking."},"authors":{"en":[{"name":"Sakaguchi Suehiro"},{"name":"Uchiyama Keiji"}],"ja":[{"name":"坂口 末廣"},{"name":"内山 圭司"}]},"description":{"en":"Conformational conversion of the cellular prion protein, PrP, into the abnormally folded isoform of prion protein, PrP, which leads to marked accumulation of PrP in brains, is a key pathogenic event in prion diseases, a group of fatal neurodegenerative disorders caused by prions. However, the exact mechanism of PrP accumulation in prion-infected neurons remains unknown. We recently reported a novel cellular mechanism to support PrP accumulation in prion-infected neurons, in which PrP itself promotes its accumulation by evading the cellular inhibitory mechanism, which is newly identified in our recent study. We showed that the VPS10P sorting receptor sortilin negatively regulates PrP accumulation in prion-infected neurons, by interacting with PrP and PrP and trafficking them to lysosomes for degradation. However, PrP stimulated lysosomal degradation of sortilin, disrupting the sortilin-mediated degradation of PrP and PrP and eventually evoking further accumulation of PrP in prion-infected neurons. These findings suggest a positive feedback amplification mechanism for PrP accumulation in prion-infected neurons.","ja":"Conformational conversion of the cellular prion protein, PrP, into the abnormally folded isoform of prion protein, PrP, which leads to marked accumulation of PrP in brains, is a key pathogenic event in prion diseases, a group of fatal neurodegenerative disorders caused by prions. However, the exact mechanism of PrP accumulation in prion-infected neurons remains unknown. We recently reported a novel cellular mechanism to support PrP accumulation in prion-infected neurons, in which PrP itself promotes its accumulation by evading the cellular inhibitory mechanism, which is newly identified in our recent study. We showed that the VPS10P sorting receptor sortilin negatively regulates PrP accumulation in prion-infected neurons, by interacting with PrP and PrP and trafficking them to lysosomes for degradation. However, PrP stimulated lysosomal degradation of sortilin, disrupting the sortilin-mediated degradation of PrP and PrP and eventually evoking further accumulation of PrP in prion-infected neurons. These findings suggest a positive feedback amplification mechanism for PrP accumulation in prion-infected neurons."},"publication_date":"2017-11-15","publication_name":{"en":"Prion","ja":"Prion"},"volume":"Vol.11","number":"No.6","starting_page":"398","ending_page":"404","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1080/19336896.2017.1391435"],"issn":["1933-690X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:19, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/110433","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/28665987","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=328699","label":"url"}],"paper_title":{"en":"Prions amplify through degradation of the VPS10P sorting receptor sortilin.","ja":"Prions amplify through degradation of the VPS10P sorting receptor sortilin."},"authors":{"en":[{"name":"Uchiyama Keiji"},{"name":"Tomita Mitsuru"},{"name":"Yano Masashi"},{"name":"Chida Junji"},{"name":"Hara Hideyuki"},{"name":"Das Rani Nandita"},{"name":"Nykjaer Anders"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"内山 圭司"},{"name":"Tomita Mitsuru"},{"name":"矢野 雅司"},{"name":"千田 淳司"},{"name":"原 英之"},{"name":"Das Rani Nandita"},{"name":"Nykjaer Anders"},{"name":"坂口 末廣"}]},"description":{"en":"Prion diseases are a group of fatal neurodegenerative disorders caused by prions, which consist mainly of the abnormally folded isoform of prion protein, PrPSc. A pivotal pathogenic event in prion disease is progressive accumulation of prions, or PrPSc, in brains through constitutive conformational conversion of the cellular prion protein, PrPC, into PrPSc. However, the cellular mechanism by which PrPSc is progressively accumulated in prion-infected neurons remains unknown. Here, we show that PrPSc is progressively accumulated in prion-infected cells through degradation of the VPS10P sorting receptor sortilin. We first show that sortilin interacts with PrPC and PrPSc and sorts them to lysosomes for degradation. Consistently, sortilin-knockdown increased PrPSc accumulation in prion-infected cells. In contrast, overexpression of sortilin reduced PrPSc accumulation in prion-infected cells. These results indicate that sortilin negatively regulates PrPSc accumulation in prion-infected cells. The negative role of sortilin in PrPSc accumulation was further confirmed in sortilin-knockout mice infected with prions. The infected mice had accelerated prion disease with early accumulation of PrPSc in their brains. Interestingly, sortilin was reduced in prion-infected cells and mouse brains. Treatment of prion-infected cells with lysosomal inhibitors, but not proteasomal inhibitors, increased the levels of sortilin. Moreover, sortilin was reduced following PrPSc becoming detectable in cells after infection with prions. These results indicate that PrPSc accumulation stimulates sortilin degradation in lysosomes. Taken together, these results show that PrPSc accumulation of itself could impair the sortilin-mediated sorting of PrPC and PrPSc to lysosomes for degradation by stimulating lysosomal degradation of sortilin, eventually leading to progressive accumulation of PrPSc in prion-infected cells.","ja":"Prion diseases are a group of fatal neurodegenerative disorders caused by prions, which consist mainly of the abnormally folded isoform of prion protein, PrPSc. A pivotal pathogenic event in prion disease is progressive accumulation of prions, or PrPSc, in brains through constitutive conformational conversion of the cellular prion protein, PrPC, into PrPSc. However, the cellular mechanism by which PrPSc is progressively accumulated in prion-infected neurons remains unknown. Here, we show that PrPSc is progressively accumulated in prion-infected cells through degradation of the VPS10P sorting receptor sortilin. We first show that sortilin interacts with PrPC and PrPSc and sorts them to lysosomes for degradation. Consistently, sortilin-knockdown increased PrPSc accumulation in prion-infected cells. In contrast, overexpression of sortilin reduced PrPSc accumulation in prion-infected cells. These results indicate that sortilin negatively regulates PrPSc accumulation in prion-infected cells. The negative role of sortilin in PrPSc accumulation was further confirmed in sortilin-knockout mice infected with prions. The infected mice had accelerated prion disease with early accumulation of PrPSc in their brains. Interestingly, sortilin was reduced in prion-infected cells and mouse brains. Treatment of prion-infected cells with lysosomal inhibitors, but not proteasomal inhibitors, increased the levels of sortilin. Moreover, sortilin was reduced following PrPSc becoming detectable in cells after infection with prions. These results indicate that PrPSc accumulation stimulates sortilin degradation in lysosomes. Taken together, these results show that PrPSc accumulation of itself could impair the sortilin-mediated sorting of PrPC and PrPSc to lysosomes for degradation by stimulating lysosomal degradation of sortilin, eventually leading to progressive accumulation of PrPSc in prion-infected cells."},"publication_date":"2017-06-30","publication_name":{"en":"PLoS Pathogens","ja":"PLoS Pathogens"},"volume":"Vol.13","number":"No.6","starting_page":"e1006470","ending_page":"e1006470","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1371/journal.ppat.1006470"],"issn":["1553-7374"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:20, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/110119","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/28255815","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85014121673&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=330317","label":"url"}],"paper_title":{"en":"Effects of prion protein devoid of the N-terminal residues 25-50 on prion pathogenesis in mice.","ja":"Effects of prion protein devoid of the N-terminal residues 25-50 on prion pathogenesis in mice."},"authors":{"en":[{"name":"Nandita Rani Das"},{"name":"Hironori Miyata"},{"name":"Hara Hideyuki"},{"name":"Uchiyama Keiji"},{"name":"Chida Junji"},{"name":"Yano Masashi"},{"name":"Hitomi Watanabe"},{"name":"Gen Kondoh"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"Nandita Rani Das"},{"name":"Hironori Miyata"},{"name":"原 英之"},{"name":"内山 圭司"},{"name":"千田 淳司"},{"name":"矢野 雅司"},{"name":"Hitomi Watanabe"},{"name":"Gen Kondoh"},{"name":"坂口 末廣"}]},"description":{"en":"The N-terminal polybasic region of the normal prion protein, PrP(C), which encompasses residues 23-31, is important for prion pathogenesis by affecting conversion of PrP(C) into the pathogenic isoform, PrP(Sc). We previously reported transgenic mice expressing PrP with residues 25-50 deleted in the PrP-null background, designated as Tg(PrPpreOR)/Prnp (0/0) mice. Here, we produced two new lines of Tg(PrPpreOR)/Prnp (0/0) mice, each expressing the mutant protein, PrPpreOR, 1.1 and 1.6 times more than PrP(C) in wild-type mice, and subsequently intracerebrally inoculated RML and 22L prions into them. The lower expresser showed slightly reduced susceptibility to RML prions but not to 22L prions. The higher expresser exhibited enhanced susceptibility to both prions. No prion transmission barrier was created in Tg(PrPpreOR)/Prnp (0/0) mice against full-length PrP(Sc). PrP(Sc)preOR accumulated in the brains of infected Tg(PrPpreOR)/Prnp (0/0) mice less than PrP(Sc) in control wild-type mice, although lower in RML-infected Tg(PrPpreOR)/Prnp (0/0) mice than in 22L-infected mice. Prion infectivity in infected Tg(PrPpreOR)/Prnp (0/0) mice was also lower than that in wild-type mice. These results indicate that deletion of residues 25-50 only slightly affects prion susceptibility, the conversion of PrP(C) into PrP(Sc), and prion infectivity in a strain-specific way. PrPpreOR retains residues 23-24 and lacks residues 25-31 in the polybasic region. It is thus conceivable that residues 23-24 rather than 25-31 are important for the polybasic region to support prion pathogenesis. However, other investigators have reported that residues 27-31 not 23-24 are important to support prion pathogenesis. Taken together, the polybasic region might support prion pathogenesis through multiple sites including residues 23-24 and 27-31.","ja":"The N-terminal polybasic region of the normal prion protein, PrP(C), which encompasses residues 23-31, is important for prion pathogenesis by affecting conversion of PrP(C) into the pathogenic isoform, PrP(Sc). We previously reported transgenic mice expressing PrP with residues 25-50 deleted in the PrP-null background, designated as Tg(PrPpreOR)/Prnp (0/0) mice. Here, we produced two new lines of Tg(PrPpreOR)/Prnp (0/0) mice, each expressing the mutant protein, PrPpreOR, 1.1 and 1.6 times more than PrP(C) in wild-type mice, and subsequently intracerebrally inoculated RML and 22L prions into them. The lower expresser showed slightly reduced susceptibility to RML prions but not to 22L prions. The higher expresser exhibited enhanced susceptibility to both prions. No prion transmission barrier was created in Tg(PrPpreOR)/Prnp (0/0) mice against full-length PrP(Sc). PrP(Sc)preOR accumulated in the brains of infected Tg(PrPpreOR)/Prnp (0/0) mice less than PrP(Sc) in control wild-type mice, although lower in RML-infected Tg(PrPpreOR)/Prnp (0/0) mice than in 22L-infected mice. Prion infectivity in infected Tg(PrPpreOR)/Prnp (0/0) mice was also lower than that in wild-type mice. These results indicate that deletion of residues 25-50 only slightly affects prion susceptibility, the conversion of PrP(C) into PrP(Sc), and prion infectivity in a strain-specific way. PrPpreOR retains residues 23-24 and lacks residues 25-31 in the polybasic region. It is thus conceivable that residues 23-24 rather than 25-31 are important for the polybasic region to support prion pathogenesis. However, other investigators have reported that residues 27-31 not 23-24 are important to support prion pathogenesis. Taken together, the polybasic region might support prion pathogenesis through multiple sites including residues 23-24 and 27-31."},"publication_date":"2017-03-02","publication_name":{"en":"Archives of Virology","ja":"Archives of Virology"},"volume":"Vol.162","number":"No.7","starting_page":"1867","ending_page":"1876","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s00705-017-3295-3"],"issn":["1432-8798"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:21, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/28077650","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=330313","label":"url"}],"paper_title":{"en":"Melanin or melanin-like substance interacts with the N-terminal portion of prion protein and inhibits abnormal prion protein formation in prion-infected cells.","ja":"Melanin or melanin-like substance interacts with the N-terminal portion of prion protein and inhibits abnormal prion protein formation in prion-infected cells."},"authors":{"en":[{"name":"Hamanaka Taichi"},{"name":"Nishizawa Keiko"},{"name":"Sakasegawa Yuji"},{"name":"Oguma Ayumi"},{"name":"Teruya Kenta"},{"name":"Kurahashi Hiroshi"},{"name":"Hara Hideyuki"},{"name":"Sakaguchi Suehiro"},{"name":"Doh-ura Katsumi"}],"ja":[{"name":"Hamanaka Taichi"},{"name":"Nishizawa Keiko"},{"name":"Sakasegawa Yuji"},{"name":"Oguma Ayumi"},{"name":"Teruya Kenta"},{"name":"Kurahashi Hiroshi"},{"name":"原 英之"},{"name":"坂口 末廣"},{"name":"Doh-ura Katsumi"}]},"description":{"en":"Prion diseases are progressive fatal neurodegenerative illnesses caused by the accumulation of transmissible abnormal prion protein (PrP). To find treatments for prion diseases, we searched for substances from natural resources that inhibit abnormal PrP formation in prion-infected cells. We found that high-molecular-weight components from insect cuticle extracts reduced abnormal PrP levels. The chemical nature of these components was consistent with that of melanin. In fact, synthetic melanin produced from tyrosine or 3-hydroxy-l-tyrosine inhibited abnormal PrP formation. Melanin did not modify cellular or cell surface PrP levels, nor did it modify lipid raft or cellular cholesterol levels. Neither did it enhance autophagy or lysosomal function. Melanin was capable of interacting with PrP at two N-terminal domains. Specifically, it strongly interacted with the PrP region of amino acids 23 to 50 including a positively charged amino acid cluster and weakly interacted with the PrP octarepeat peptide region of residues 51 to 90. However, the in vitro and in vivo data were inconsistent with those of prion-infected cells. Abnormal PrP formation in protein misfolding cyclic amplification was not inhibited by melanin. Survival after prion infection was not significantly altered in albino mice or exogenously melanin-injected mice compared with that of control mice. These data suggest that melanin, a main determinant of skin color, is not likely to modify prion disease pathogenesis, even though racial differences in the incidence of human prion diseases have been reported. Thus, the findings identify an interaction between melanin and the N terminus of PrP, but the pathophysiological roles of the PrP-melanin interaction remain unclear.IMPORTANCE The N-terminal region of PrP is reportedly important for neuroprotection, neurotoxicity, and abnormal PrP formation, as this region is bound by many factors, such as metal ions, lipids, nucleic acids, antiprion compounds, and several proteins, including abnormal PrP in prion disease and the Aβ oligomer in Alzheimer's disease. In the present study, melanin, a main determinant of skin color, was newly found to interact with this N-terminal region and inhibits abnormal PrP formation in prion-infected cells. However, the data for prion infection in mice lacking melanin production suggest that melanin is not associated with the prion disease mechanism, although the incidence of prion disease is reportedly much higher in white people than in black people. Thus, the roles of the PrP-melanin interaction remain to be further elucidated, but melanin might be a useful competitive tool for evaluating the functions of other ligands at the N-terminal region.","ja":"Prion diseases are progressive fatal neurodegenerative illnesses caused by the accumulation of transmissible abnormal prion protein (PrP). To find treatments for prion diseases, we searched for substances from natural resources that inhibit abnormal PrP formation in prion-infected cells. We found that high-molecular-weight components from insect cuticle extracts reduced abnormal PrP levels. The chemical nature of these components was consistent with that of melanin. In fact, synthetic melanin produced from tyrosine or 3-hydroxy-l-tyrosine inhibited abnormal PrP formation. Melanin did not modify cellular or cell surface PrP levels, nor did it modify lipid raft or cellular cholesterol levels. Neither did it enhance autophagy or lysosomal function. Melanin was capable of interacting with PrP at two N-terminal domains. Specifically, it strongly interacted with the PrP region of amino acids 23 to 50 including a positively charged amino acid cluster and weakly interacted with the PrP octarepeat peptide region of residues 51 to 90. However, the in vitro and in vivo data were inconsistent with those of prion-infected cells. Abnormal PrP formation in protein misfolding cyclic amplification was not inhibited by melanin. Survival after prion infection was not significantly altered in albino mice or exogenously melanin-injected mice compared with that of control mice. These data suggest that melanin, a main determinant of skin color, is not likely to modify prion disease pathogenesis, even though racial differences in the incidence of human prion diseases have been reported. Thus, the findings identify an interaction between melanin and the N terminus of PrP, but the pathophysiological roles of the PrP-melanin interaction remain unclear.IMPORTANCE The N-terminal region of PrP is reportedly important for neuroprotection, neurotoxicity, and abnormal PrP formation, as this region is bound by many factors, such as metal ions, lipids, nucleic acids, antiprion compounds, and several proteins, including abnormal PrP in prion disease and the Aβ oligomer in Alzheimer's disease. In the present study, melanin, a main determinant of skin color, was newly found to interact with this N-terminal region and inhibits abnormal PrP formation in prion-infected cells. However, the data for prion infection in mice lacking melanin production suggest that melanin is not associated with the prion disease mechanism, although the incidence of prion disease is reportedly much higher in white people than in black people. Thus, the roles of the PrP-melanin interaction remain to be further elucidated, but melanin might be a useful competitive tool for evaluating the functions of other ligands at the N-terminal region."},"publication_date":"2017-01-11","publication_name":{"en":"Journal of Virology","ja":"Journal of Virology"},"volume":"Vol.91","number":"No.6","starting_page":"e01862","ending_page":"16","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1128/JVI.01862-16"],"issn":["1098-5514"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:22, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=307768","label":"url"}],"paper_title":{"en":"Prion Protein Binds to Aldolase A Produced by Bovine Intestinal M Cells.","ja":"Prion Protein Binds to Aldolase A Produced by Bovine Intestinal M Cells."},"authors":{"en":[{"name":"Nagasawa Yuya"},{"name":"Takahashi Yu"},{"name":"Itani Wataru"},{"name":"Watanabe Hitoshi"},{"name":"Hidaka Yusuke"},{"name":"Morita Shotaro"},{"name":"Suzuki Kei"},{"name":"Watanabe Kouichi"},{"name":"Ohwada Shyuichi"},{"name":"Kitazawa Haruki"},{"name":"Imamura Morikazu"},{"name":"Yokoyama Takashi"},{"name":"Horiuchi Motohiro"},{"name":"Sakaguchi Suehiro"},{"name":"Mohri Shirou"},{"name":"Rose T. Michael"},{"name":"Nochi Tomonori"},{"name":"Aso Hisashi"}],"ja":[{"name":"Nagasawa Yuya"},{"name":"Takahashi Yu"},{"name":"Itani Wataru"},{"name":"Watanabe Hitoshi"},{"name":"Hidaka Yusuke"},{"name":"Morita Shotaro"},{"name":"Suzuki Kei"},{"name":"Watanabe Kouichi"},{"name":"Ohwada Shyuichi"},{"name":"Kitazawa Haruki"},{"name":"Imamura Morikazu"},{"name":"Yokoyama Takashi"},{"name":"Horiuchi Motohiro"},{"name":"坂口 末廣"},{"name":"Mohri Shirou"},{"name":"Rose T. Michael"},{"name":"Nochi Tomonori"},{"name":"Aso Hisashi"}]},"publication_date":"2015-03-11","publication_name":{"en":"Open Journal of Veterinary Medicine","ja":"Open Journal of Veterinary Medicine"},"volume":"Vol.5","number":"No.3","starting_page":"43","ending_page":"60","languages":["eng"],"referee":true,"identifiers":{"doi":["10.4236/ojvm.2015.53007"],"issn":["2165-3356"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:23, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/25330286","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=286966","label":"url"}],"paper_title":{"en":"Mouse-Hamster Chimeric Prion Protein (PrP) Devoid of N-terminal Residues 23-88 Restores Susceptibility to 22L Prions, But Not to RML Prions in PrP-Knockout Mice.","ja":"Mouse-Hamster Chimeric Prion Protein (PrP) Devoid of N-terminal Residues 23-88 Restores Susceptibility to 22L Prions, But Not to RML Prions in PrP-Knockout Mice."},"authors":{"en":[{"name":"Uchiyama Keiji"},{"name":"Hironori Miyata"},{"name":"Yano Masashi"},{"name":"Yamaguti Yoshitaka"},{"name":"Morikazu Imamura"},{"name":"Naomi Muramatsu"},{"name":"Nandita Rani Das"},{"name":"Chida Junji"},{"name":"Hara Hideyuki"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"内山 圭司"},{"name":"Hironori Miyata"},{"name":"矢野 雅司"},{"name":"山口 仁孝"},{"name":"Morikazu Imamura"},{"name":"村松 直美"},{"name":"Nandita Rani Das"},{"name":"千田 淳司"},{"name":"原 英之"},{"name":"坂口 末廣"}]},"description":{"en":"Prion infection induces conformational conversion of the normal prion protein PrPC, into the pathogenic isoform PrPSc, in prion diseases. It has been shown that PrP-knockout (Prnp0/0) mice transgenically reconstituted with a mouse-hamster chimeric PrP lacking N-terminal residues 23-88, or Tg(MHM223-88)/Prnp 0/0 mice, neither developed the disease nor accumulated MHM2Sc23-88 in their brains after inoculation with RML prions. In contrast, RML-inoculated Tg(MHM223-88)/Prnp 0/+ mice developed the disease with abundant accumulation of MHM2Sc23-88 in their brains. These results indicate that MHM223-88 itself might either lose or greatly reduce the converting capacity to MHM2Sc23-88, and that the co-expressing wild-type PrPC can stimulate the conversion of MHM223-88 to MHM2Sc23-88 in trans. In the present study, we confirmed that Tg(MHM223-88)/Prnp 0/0 mice remained resistant to RML prions for up to 730 days after inoculation. However, we found that Tg(MHM223-88)/Prnp 0/0 mice were susceptible to 22L prions, developing the disease with prolonged incubation times and accumulating MHM2Sc23-88 in their brains. We also found accelerated conversion of MHM223-88 into MHM2Sc23-88 in the brains of RML- and 22L-inoculated Tg(MHM223-88)/Prnp 0/+ mice. However, wild-type PrPSc accumulated less in the brains of these inoculated Tg(MHM223-88)/Prnp 0/+ mice, compared with RML- and 22L-inoculated Prnp 0/+ mice. These results show that MHM223-88 itself can convert into MHM2Sc23-88 without the help of the trans-acting PrPC, and that, irrespective of prion strains inoculated, the co-expressing wild-type PrPC stimulates the conversion of MHM223-88 into MHM2Sc23-88, but to the contrary, the co-expressing MHM223-88 disturbs the conversion of wild-type PrPC into PrPSc.","ja":"Prion infection induces conformational conversion of the normal prion protein PrPC, into the pathogenic isoform PrPSc, in prion diseases. It has been shown that PrP-knockout (Prnp0/0) mice transgenically reconstituted with a mouse-hamster chimeric PrP lacking N-terminal residues 23-88, or Tg(MHM223-88)/Prnp 0/0 mice, neither developed the disease nor accumulated MHM2Sc23-88 in their brains after inoculation with RML prions. In contrast, RML-inoculated Tg(MHM223-88)/Prnp 0/+ mice developed the disease with abundant accumulation of MHM2Sc23-88 in their brains. These results indicate that MHM223-88 itself might either lose or greatly reduce the converting capacity to MHM2Sc23-88, and that the co-expressing wild-type PrPC can stimulate the conversion of MHM223-88 to MHM2Sc23-88 in trans. In the present study, we confirmed that Tg(MHM223-88)/Prnp 0/0 mice remained resistant to RML prions for up to 730 days after inoculation. However, we found that Tg(MHM223-88)/Prnp 0/0 mice were susceptible to 22L prions, developing the disease with prolonged incubation times and accumulating MHM2Sc23-88 in their brains. We also found accelerated conversion of MHM223-88 into MHM2Sc23-88 in the brains of RML- and 22L-inoculated Tg(MHM223-88)/Prnp 0/+ mice. However, wild-type PrPSc accumulated less in the brains of these inoculated Tg(MHM223-88)/Prnp 0/+ mice, compared with RML- and 22L-inoculated Prnp 0/+ mice. These results show that MHM223-88 itself can convert into MHM2Sc23-88 without the help of the trans-acting PrPC, and that, irrespective of prion strains inoculated, the co-expressing wild-type PrPC stimulates the conversion of MHM223-88 into MHM2Sc23-88, but to the contrary, the co-expressing MHM223-88 disturbs the conversion of wild-type PrPC into PrPSc."},"publication_date":"2014-10-16","publication_name":{"en":"PLoS ONE","ja":"PLoS ONE"},"volume":"Vol.9","number":"No.10","starting_page":"e109737","ending_page":"e109737","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1371/journal.pone.0109737"],"issn":["1932-6203"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:24, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/24335150","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-84893871953&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=273979","label":"url"}],"paper_title":{"en":"Disturbed vesicular trafficking of membrane proteins in prion disease.","ja":"Disturbed vesicular trafficking of membrane proteins in prion disease."},"authors":{"en":[{"name":"Uchiyama Keiji"},{"name":"Hironori Miyata"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"内山 圭司"},{"name":"Hironori Miyata"},{"name":"坂口 末廣"}]},"description":{"en":"The pathogenic mechanism of prion diseases remains unknown. We recently reported that prion infection disturbs post-Golgi trafficking of certain types of membrane proteins to the cell surface, resulting in reduced surface expression of membrane proteins and abrogating the signal from the proteins. The surface expression of the membrane proteins was reduced in the brains of mice inoculated with prions, well before abnormal symptoms became evident. Prions or pathogenic prion proteins were mainly detected in endosomal compartments, being particularly abundant in recycling endosomes. Some newly synthesized membrane proteins are delivered to the surface from the Golgi apparatus through recycling endosomes, and some endocytosed membrane proteins are delivered back to the surface through recycling endosomes. These results suggest that prions might cause neuronal dysfunctions and cell loss by disturbing post-Golgi trafficking of membrane proteins via accumulation in recycling endosomes. Interestingly, it was recently shown that delivery of a calcium channel protein to the cell surface was impaired and its function was abrogated in a mouse model of hereditary prion disease. Taken together, these results suggest that impaired delivery of membrane proteins to the cell surface is a common pathogenic event in acquired and hereditary prion diseases.","ja":"The pathogenic mechanism of prion diseases remains unknown. We recently reported that prion infection disturbs post-Golgi trafficking of certain types of membrane proteins to the cell surface, resulting in reduced surface expression of membrane proteins and abrogating the signal from the proteins. The surface expression of the membrane proteins was reduced in the brains of mice inoculated with prions, well before abnormal symptoms became evident. Prions or pathogenic prion proteins were mainly detected in endosomal compartments, being particularly abundant in recycling endosomes. Some newly synthesized membrane proteins are delivered to the surface from the Golgi apparatus through recycling endosomes, and some endocytosed membrane proteins are delivered back to the surface through recycling endosomes. These results suggest that prions might cause neuronal dysfunctions and cell loss by disturbing post-Golgi trafficking of membrane proteins via accumulation in recycling endosomes. Interestingly, it was recently shown that delivery of a calcium channel protein to the cell surface was impaired and its function was abrogated in a mouse model of hereditary prion disease. Taken together, these results suggest that impaired delivery of membrane proteins to the cell surface is a common pathogenic event in acquired and hereditary prion diseases."},"publication_date":"2013-12-11","publication_name":{"en":"Prion","ja":"Prion"},"volume":"Vol.7","number":"No.6","starting_page":"447","ending_page":"451","languages":["eng"],"referee":true,"identifiers":{"doi":["10.4161/pri.27381"],"issn":["1933-690X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:25, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://ci.nii.ac.jp/naid/120006985917/","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/23593266","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1050850247205350016/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=271183","label":"url"}],"paper_title":{"en":"Age-dependent impairment of eyeblink conditioning in prion protein-deficient mice.","ja":"Age-dependent impairment of eyeblink conditioning in prion protein-deficient mice."},"authors":{"en":[{"name":"Yaushi Kishimoto"},{"name":"Moritoshi Hirono"},{"name":"Ryuichiro Atarashi"},{"name":"Sakaguchi Suehiro"},{"name":"Tohru Yoshioka"},{"name":"Shigeru Katamine"},{"name":"Yutaka Kirino"}],"ja":[{"name":"Yaushi Kishimoto"},{"name":"Moritoshi Hirono"},{"name":"Ryuichiro Atarashi"},{"name":"坂口 末廣"},{"name":"Tohru Yoshioka"},{"name":"Shigeru Katamine"},{"name":"Yutaka Kirino"}]},"description":{"en":"Mice lacking the prion protein (PrPC) gene (Prnp), Ngsk Prnp0/0 mice, show late-onset cerebellar Purkinje cell (PC) degeneration because of ectopic overexpression of PrPC-like protein (PrPLP/Dpl). Because PrPC is highly expressed in cerebellar neurons (including PCs and granule cells), it may be involved in cerebellar synaptic function and cerebellar cognitive function. However, no studies have been conducted to investigate the possible involvement of PrPC and/or PrPLP/Dpl in cerebellum-dependent discrete motor learning. Therefore, the present cross-sectional study was designed to examine cerebellum-dependent delay eyeblink conditioning in Ngsk Prnp0/0 mice in adulthood (16, 40, and 60 weeks of age). The aims of the present study were two-fold: (1) to examine the role of PrPC and/or PrPLP/Dpl in cerebellum-dependent motor learning and (2) to confirm the age-related deterioration of eyeblink conditioning in Ngsk Prnp0/0 mice as an animal model of progressive cerebellar degeneration. Ngsk Prnp0/0 mice aged 16 weeks exhibited intact acquisition of conditioned eyeblink responses (CRs), although the CR timing was altered. The same result was observed in another line of PrPc-deficient mice, ZrchI PrnP0/0 mice. However, at 40 weeks of age, CR incidence impairment was observed in Ngsk Prnp0/0 mice. Furthermore, Ngsk Prnp0/0 mice aged 60 weeks showed more significantly impaired CR acquisition than Ngsk Prnp0/0 mice aged 40 weeks, indicating the temporal correlation between cerebellar PC degeneration and motor learning deficits. Our findings indicate the importance of the cerebellar cortex in delay eyeblink conditioning and suggest an important physiological role of prion protein in cerebellar motor learning.","ja":"Mice lacking the prion protein (PrPC) gene (Prnp), Ngsk Prnp0/0 mice, show late-onset cerebellar Purkinje cell (PC) degeneration because of ectopic overexpression of PrPC-like protein (PrPLP/Dpl). Because PrPC is highly expressed in cerebellar neurons (including PCs and granule cells), it may be involved in cerebellar synaptic function and cerebellar cognitive function. However, no studies have been conducted to investigate the possible involvement of PrPC and/or PrPLP/Dpl in cerebellum-dependent discrete motor learning. Therefore, the present cross-sectional study was designed to examine cerebellum-dependent delay eyeblink conditioning in Ngsk Prnp0/0 mice in adulthood (16, 40, and 60 weeks of age). The aims of the present study were two-fold: (1) to examine the role of PrPC and/or PrPLP/Dpl in cerebellum-dependent motor learning and (2) to confirm the age-related deterioration of eyeblink conditioning in Ngsk Prnp0/0 mice as an animal model of progressive cerebellar degeneration. Ngsk Prnp0/0 mice aged 16 weeks exhibited intact acquisition of conditioned eyeblink responses (CRs), although the CR timing was altered. The same result was observed in another line of PrPc-deficient mice, ZrchI PrnP0/0 mice. However, at 40 weeks of age, CR incidence impairment was observed in Ngsk Prnp0/0 mice. Furthermore, Ngsk Prnp0/0 mice aged 60 weeks showed more significantly impaired CR acquisition than Ngsk Prnp0/0 mice aged 40 weeks, indicating the temporal correlation between cerebellar PC degeneration and motor learning deficits. Our findings indicate the importance of the cerebellar cortex in delay eyeblink conditioning and suggest an important physiological role of prion protein in cerebellar motor learning."},"publication_date":"2013-10-10","publication_name":{"en":"PLoS ONE","ja":"PLoS ONE"},"volume":"Vol.8","number":"No.4","starting_page":"e60627","ending_page":"e60627","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1371/journal.pone.0060627"],"issn":["1932-6203"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:26, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/23712919","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-84879844540&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=271190","label":"url"}],"paper_title":{"en":"Synthesis of an (11) C-labeled antiprion GN8 derivative and evaluation of its brain uptake by positron emission tomography.","ja":"Synthesis of an (11) C-labeled antiprion GN8 derivative and evaluation of its brain uptake by positron emission tomography."},"authors":{"en":[{"name":"Tsutomu Kimura"},{"name":"Takeo Sako"},{"name":"Siqin"},{"name":"Junji Hosokawa-Muto"},{"name":"Yi Long Cui"},{"name":"Yasuhiro Wada"},{"name":"Yosky Kataoka"},{"name":"Hisashi Doi"},{"name":"Sakaguchi Suehiro"},{"name":"Masaaki Suzuki"},{"name":"Yasuyoshi Watanabe"},{"name":"Kazuo Kuwata"}],"ja":[{"name":"Tsutomu Kimura"},{"name":"Takeo Sako"},{"name":"Siqin"},{"name":"Junji Hosokawa-Muto"},{"name":"Yi Long Cui"},{"name":"Yasuhiro Wada"},{"name":"Yosky Kataoka"},{"name":"Hisashi Doi"},{"name":"坂口 末廣"},{"name":"Masaaki Suzuki"},{"name":"Yasuyoshi Watanabe"},{"name":"Kazuo Kuwata"}]},"description":{"en":"A radiolabeled PET! A (11) C-labeled derivative of N,N'-(methylenedi-4,1-phenylene)bis[2-(1-pyrrolidinyl) acetamide] (GN8), an antiprion agent currently under development, was synthesized by palladium-catalyzed rapid methylation of aryltributylstannane and assessed for brain penetration and organ distribution in rats by positron emission tomography (PET).","ja":"A radiolabeled PET! A (11) C-labeled derivative of N,N'-(methylenedi-4,1-phenylene)bis[2-(1-pyrrolidinyl) acetamide] (GN8), an antiprion agent currently under development, was synthesized by palladium-catalyzed rapid methylation of aryltributylstannane and assessed for brain penetration and organ distribution in rats by positron emission tomography (PET)."},"publication_date":"2013-07","publication_name":{"en":"ChemMedChem","ja":"ChemMedChem"},"volume":"Vol.8","number":"No.7","starting_page":"1035","ending_page":"1039","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1002/cmdc.201300167"],"issn":["1860-7187"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:27, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/23673631","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=268337","label":"url"}],"paper_title":{"en":"Prions disturb post-Golgi trafficking of membrane proteins.","ja":"Prions disturb post-Golgi trafficking of membrane proteins."},"authors":{"en":[{"name":"Uchiyama Keiji"},{"name":"Muramatsu Naomi"},{"name":"Yano Masashi"},{"name":"Usui Takeshi"},{"name":"Miyata Hironori"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"内山 圭司"},{"name":"Muramatsu Naomi"},{"name":"矢野 雅司"},{"name":"Usui Takeshi"},{"name":"Miyata Hironori"},{"name":"坂口 末廣"}]},"description":{"en":"Conformational conversion of normal cellular prion protein PrP(C) into pathogenic PrP(Sc) is central to the pathogenesis of prion diseases. However, the pathogenic mechanism remains unknown. Here we show that post-Golgi vesicular trafficking is significantly delayed in prion-infected N2a cells. Accordingly, cell surface expression of membrane proteins examined, including PrP(C), insulin receptor involved in neuroprotection, and attractin, whose mutation causes prion disease-like spongiform neurodegeneration, is reduced. Instead, they accumulate in the Golgi apparatus. PrP(Sc) is detected throughout endosomal compartments, being particularly abundant in recycling endosome. We also show reduced surface expression of PrP(C) and insulin receptor in prion-infected mouse brains well before the onset of disease. These results suggest that prion infection might impair post-Golgi trafficking of membrane proteins to the cell surface in neurons via PrP(Sc) accumulated in recycling endosome, and eventually induce neuronal dysfunctions associated with prion diseases.","ja":"Conformational conversion of normal cellular prion protein PrP(C) into pathogenic PrP(Sc) is central to the pathogenesis of prion diseases. However, the pathogenic mechanism remains unknown. Here we show that post-Golgi vesicular trafficking is significantly delayed in prion-infected N2a cells. Accordingly, cell surface expression of membrane proteins examined, including PrP(C), insulin receptor involved in neuroprotection, and attractin, whose mutation causes prion disease-like spongiform neurodegeneration, is reduced. Instead, they accumulate in the Golgi apparatus. PrP(Sc) is detected throughout endosomal compartments, being particularly abundant in recycling endosome. We also show reduced surface expression of PrP(C) and insulin receptor in prion-infected mouse brains well before the onset of disease. These results suggest that prion infection might impair post-Golgi trafficking of membrane proteins to the cell surface in neurons via PrP(Sc) accumulated in recycling endosome, and eventually induce neuronal dysfunctions associated with prion diseases."},"publication_date":"2013-05-14","publication_name":{"en":"Nature Communications","ja":"Nature Communications"},"volume":"Vol.4","starting_page":"1846","ending_page":"1846","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/ncomms2873"],"issn":["2041-1723"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:28, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/22927985","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=267754","label":"url"}],"paper_title":{"en":"Biological and biochemical characterization of mice expressing prion protein devoid of the octapeptide repeat region after infection with prions.","ja":"Biological and biochemical characterization of mice expressing prion protein devoid of the octapeptide repeat region after infection with prions."},"authors":{"en":[{"name":"Yamaguti Yoshitaka"},{"name":"Miyata Hironori"},{"name":"Uchiyama Keiji"},{"name":"Ootsuyama Akira"},{"name":"Inubushi Sachiko"},{"name":"Mori Tsuyoshi"},{"name":"Muramatsu Naomi"},{"name":"Katamine Shigeru"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"山口 仁孝"},{"name":"Miyata Hironori"},{"name":"内山 圭司"},{"name":"Ootsuyama Akira"},{"name":"犬伏 祥子"},{"name":"森 剛志"},{"name":"Muramatsu Naomi"},{"name":"Katamine Shigeru"},{"name":"坂口 末廣"}]},"description":{"en":"Accumulating lines of evidence indicate that the N-terminal domain of prion protein (PrP) is involved in prion susceptibility in mice. In this study, to investigate the role of the octapeptide repeat (OR) region alone in the N-terminal domain for the susceptibility and pathogenesis of prion disease, we intracerebrally inoculated RML scrapie prions into tg(PrPOR)/Prnp(0/0) mice, which express mouse PrP missing only the OR region on the PrP-null background. Incubation times of these mice were not extended. Protease-resistant PrPOR, or PrP(Sc)OR, was easily detectable but lower in the brains of these mice, compared to that in control wild-type mice. Consistently, prion titers were slightly lower and astrogliosis was milder in their brains. However, in their spinal cords, PrP(Sc)OR and prion titers were abundant and astrogliosis was as strong as in control wild-type mice. These results indicate that the role of the OR region in prion susceptibility and pathogenesis of the disease is limited. We also found that the PrP(Sc)OR, including the pre-OR residues 23-50, was unusually protease-resistant, indicating that deletion of the OR region could cause structural changes to the pre-OR region upon prion infection, leading to formation of a protease-resistant structure for the pre-OR region.","ja":"Accumulating lines of evidence indicate that the N-terminal domain of prion protein (PrP) is involved in prion susceptibility in mice. In this study, to investigate the role of the octapeptide repeat (OR) region alone in the N-terminal domain for the susceptibility and pathogenesis of prion disease, we intracerebrally inoculated RML scrapie prions into tg(PrPOR)/Prnp(0/0) mice, which express mouse PrP missing only the OR region on the PrP-null background. Incubation times of these mice were not extended. Protease-resistant PrPOR, or PrP(Sc)OR, was easily detectable but lower in the brains of these mice, compared to that in control wild-type mice. Consistently, prion titers were slightly lower and astrogliosis was milder in their brains. However, in their spinal cords, PrP(Sc)OR and prion titers were abundant and astrogliosis was as strong as in control wild-type mice. These results indicate that the role of the OR region in prion susceptibility and pathogenesis of the disease is limited. We also found that the PrP(Sc)OR, including the pre-OR residues 23-50, was unusually protease-resistant, indicating that deletion of the OR region could cause structural changes to the pre-OR region upon prion infection, leading to formation of a protease-resistant structure for the pre-OR region."},"publication_date":"2012-08-21","publication_name":{"en":"PLoS ONE","ja":"PLoS ONE"},"volume":"Vol.7","number":"No.8","starting_page":"e43540","ending_page":"e43540","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1371/journal.pone.0043540"],"issn":["1932-6203"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:29, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/22356913","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=255167","label":"url"}],"paper_title":{"en":"Direct evidence of generation and accumulation of -sheet-rich prion protein in scrapie-infected neuroblastoma cells with human IgG1 antibody specific for -form prion protein.","ja":"Direct evidence of generation and accumulation of -sheet-rich prion protein in scrapie-infected neuroblastoma cells with human IgG1 antibody specific for -form prion protein."},"authors":{"en":[{"name":"Kubota Toshiya"},{"name":"Hamazoe Yuta"},{"name":"Hashiguchi Shuhei"},{"name":"Ishibashi Daisuke"},{"name":"Akasaka Kazuyuki"},{"name":"Nishida Noriyuki"},{"name":"Katamine Shigeru"},{"name":"Sakaguchi Suehiro"},{"name":"Kuroki Ryota"},{"name":"Nakashima Toshihiro"},{"name":"Sugimura Kazuhisa"}],"ja":[{"name":"Kubota Toshiya"},{"name":"Hamazoe Yuta"},{"name":"Hashiguchi Shuhei"},{"name":"Ishibashi Daisuke"},{"name":"Akasaka Kazuyuki"},{"name":"Nishida Noriyuki"},{"name":"Katamine Shigeru"},{"name":"坂口 末廣"},{"name":"Kuroki Ryota"},{"name":"Nakashima Toshihiro"},{"name":"Sugimura Kazuhisa"}]},"description":{"en":"We prepared -sheet-rich recombinant full-length prion protein (-form PrP) (Jackson, G. S., Hosszu, L. L., Power, A., Hill, A. F., Kenney, J., Saibil, H., Craven, C. J., Waltho, J. P., Clarke, A. R., and Collinge, J. (1999) Science 283, 1935-1937). Using this -form PrP and a human single chain Fv-displaying phage library, we have established a human IgG1 antibody specific to -form but not -form PrP, PRB7 IgG. When prion-infected ScN2a cells were cultured with PRB7 IgG, they generated and accumulated PRB7-binding granules in the cytoplasm with time, consequently becoming apoptotic cells bearing very large PRB7-bound aggregates. The SAF32 antibody recognizing the N-terminal octarepeat region of full-length PrP stained distinct granules in these cells as determined by confocal laser microscopy observation. When the accumulation of proteinase K-resistant PrP was examined in prion-infected ScN2a cells cultured in the presence of PRB7 IgG or SAF32, it was strongly inhibited by SAF32 but not at all by PRB7 IgG. Thus, we demonstrated direct evidence of the generation and accumulation of -sheet-rich PrP in ScN2a cells de novo. These results suggest first that PRB7-bound PrP is not responsible for the accumulation of -form PrP aggregates, which are rather an end product resulting in the triggering of apoptotic cell death, and second that SAF32-bound PrP lacking the PRB7-recognizing -form may represent so-called PrP(Sc) with prion propagation activity. PRB7 is the first human antibody specific to -form PrP and has become a powerful tool for the characterization of the biochemical nature of prion and its pathology.","ja":"We prepared -sheet-rich recombinant full-length prion protein (-form PrP) (Jackson, G. S., Hosszu, L. L., Power, A., Hill, A. F., Kenney, J., Saibil, H., Craven, C. J., Waltho, J. P., Clarke, A. R., and Collinge, J. (1999) Science 283, 1935-1937). Using this -form PrP and a human single chain Fv-displaying phage library, we have established a human IgG1 antibody specific to -form but not -form PrP, PRB7 IgG. When prion-infected ScN2a cells were cultured with PRB7 IgG, they generated and accumulated PRB7-binding granules in the cytoplasm with time, consequently becoming apoptotic cells bearing very large PRB7-bound aggregates. The SAF32 antibody recognizing the N-terminal octarepeat region of full-length PrP stained distinct granules in these cells as determined by confocal laser microscopy observation. When the accumulation of proteinase K-resistant PrP was examined in prion-infected ScN2a cells cultured in the presence of PRB7 IgG or SAF32, it was strongly inhibited by SAF32 but not at all by PRB7 IgG. Thus, we demonstrated direct evidence of the generation and accumulation of -sheet-rich PrP in ScN2a cells de novo. These results suggest first that PRB7-bound PrP is not responsible for the accumulation of -form PrP aggregates, which are rather an end product resulting in the triggering of apoptotic cell death, and second that SAF32-bound PrP lacking the PRB7-recognizing -form may represent so-called PrP(Sc) with prion propagation activity. PRB7 is the first human antibody specific to -form PrP and has become a powerful tool for the characterization of the biochemical nature of prion and its pathology."},"publication_date":"2012-02-22","publication_name":{"en":"The Journal of Biological Chemistry","ja":"The Journal of Biological Chemistry"},"volume":"Vol.287","number":"No.17","starting_page":"14023","ending_page":"14039","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1074/jbc.M111.318352"],"issn":["1083-351X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:30, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/22008817","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=245271","label":"url"}],"paper_title":{"en":"Antigenic mimicry-mediated anti-prion effects induced by bacterial enzyme succinylarginine dihydrolase in mice.","ja":"Antigenic mimicry-mediated anti-prion effects induced by bacterial enzyme succinylarginine dihydrolase in mice."},"authors":{"en":[{"name":"Daisuke Ishibashi"},{"name":"Hitoki Yamanaka"},{"name":"Mori Tsuyoshi"},{"name":"Naohiro Yamaguchi"},{"name":"Yamaguti Yoshitaka"},{"name":"Noriyuki Nishida"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"Daisuke Ishibashi"},{"name":"Hitoki Yamanaka"},{"name":"森 剛志"},{"name":"Naohiro Yamaguchi"},{"name":"山口 仁孝"},{"name":"Noriyuki Nishida"},{"name":"坂口 末廣"}]},"description":{"en":"Prions, the causative agents of prion diseases, are immunologically tolerated because their major component, prion protein (PrP), is a host-encoded molecule. Therefore, no effective prion vaccines have been developed. We previously showed that heterologous bovine and sheep PrP immunizations of mice overcame tolerance by an antigenic mimicry mechanism to efficiently induce anti-PrP auto-antibodies (Abs), significantly prolonging incubation times in mice subsequently infected with the mouse-adapted Fukuoka-1 prion. These results prompted us to investigate if non-mammal derived molecules able to antigenically mimic anti-prion epitopes, could act as prion vaccines. We show here that immunization of mice with recombinant succinylarginine dihydrolase, a bacterial enzyme with a peptide sequence similar to an anti-prion epitope, induced anti-PrP auto-Abs with anti-prion activity and significantly retarded survival times of the mice subsequently infected with Fukuoka-1 prions. These results might open a way for development of a new type of antigenic mimicry-based prion vaccine.","ja":"Prions, the causative agents of prion diseases, are immunologically tolerated because their major component, prion protein (PrP), is a host-encoded molecule. Therefore, no effective prion vaccines have been developed. We previously showed that heterologous bovine and sheep PrP immunizations of mice overcame tolerance by an antigenic mimicry mechanism to efficiently induce anti-PrP auto-antibodies (Abs), significantly prolonging incubation times in mice subsequently infected with the mouse-adapted Fukuoka-1 prion. These results prompted us to investigate if non-mammal derived molecules able to antigenically mimic anti-prion epitopes, could act as prion vaccines. We show here that immunization of mice with recombinant succinylarginine dihydrolase, a bacterial enzyme with a peptide sequence similar to an anti-prion epitope, induced anti-PrP auto-Abs with anti-prion activity and significantly retarded survival times of the mice subsequently infected with Fukuoka-1 prions. These results might open a way for development of a new type of antigenic mimicry-based prion vaccine."},"publication_date":"2011-10-18","publication_name":{"en":"Vaccine","ja":"Vaccine"},"volume":"Vol.29","number":"No.50","starting_page":"9321","ending_page":"9328","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.vaccine.2011.10.017"],"issn":["1873-2518"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:31, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21763679","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=239739","label":"url"}],"paper_title":{"en":"Orally administered prion protein is incorporated by m cells and spreads into lymphoid tissues with macrophages in prion protein knockout mice.","ja":"Orally administered prion protein is incorporated by m cells and spreads into lymphoid tissues with macrophages in prion protein knockout mice."},"authors":{"en":[{"name":"Takakura Ikuro"},{"name":"Miyazawa Kohtaro"},{"name":"Kanaya Takashi"},{"name":"Itani Wataru"},{"name":"Watanabe Kouichi"},{"name":"Ohwada Shyuichi"},{"name":"Watanabe Hitoshi"},{"name":"Hondo Tetsuya"},{"name":"Rose Michael T"},{"name":"Mori Tsuyoshi"},{"name":"Sakaguchi Suehiro"},{"name":"Nishida Noriyuki"},{"name":"Katamine Shigeru"},{"name":"Yamaguchi Takahiro"},{"name":"Aso Hisashi"}],"ja":[{"name":"Takakura Ikuro"},{"name":"Miyazawa Kohtaro"},{"name":"Kanaya Takashi"},{"name":"Itani Wataru"},{"name":"Watanabe Kouichi"},{"name":"Ohwada Shyuichi"},{"name":"Watanabe Hitoshi"},{"name":"Hondo Tetsuya"},{"name":"Rose Michael T"},{"name":"森 剛志"},{"name":"坂口 末廣"},{"name":"Nishida Noriyuki"},{"name":"Katamine Shigeru"},{"name":"Yamaguchi Takahiro"},{"name":"Aso Hisashi"}]},"description":{"en":"Transmissible spongiform encephalopathies are fatal neurodegenerative diseases. Infection by the oral route is assumed to be important, although its pathogenesis is not understood. Using prion protein (PrP) knockout mice, we investigated the sequence of events during the invasion of orally administered PrPs through the intestinal mucosa and the spread into lymphoid tissues and the peripheral nervous system. Orally administered PrPs were incorporated by intestinal epitheliocytes in the follicle-associated epithelium and villi within 1 hour. PrP-positive cells accumulated in the subfollicle region of Peyer's patches a few hours thereafter. PrP-positive cells spread toward the mesenteric lymph nodes and spleen after the accumulation of PrPs in the Peyer's patches. The number of PrP molecules in the mesenteric lymph nodes and spleen peaked at 2 days and 6 days after inoculation, respectively. The epitheliocytes in the follicle-associated epithelium incorporating PrPs were annexin V-positive microfold cells and PrP-positive cells in Peyer's patches and spleen were CD11b-positive and CD14-positive macrophages. Additionally, PrP-positive cells in Peyer's patches and spleen were detected in the vicinity of peripheral nerve fibers in the early stages of infection. These results indicate that orally delivered PrPs were incorporated by microfold cells promptly after challenge and that macrophages might act as a transporter of incorporated PrPs from the Peyer's patches to other lymphoid tissues and the peripheral nervous system.","ja":"Transmissible spongiform encephalopathies are fatal neurodegenerative diseases. Infection by the oral route is assumed to be important, although its pathogenesis is not understood. Using prion protein (PrP) knockout mice, we investigated the sequence of events during the invasion of orally administered PrPs through the intestinal mucosa and the spread into lymphoid tissues and the peripheral nervous system. Orally administered PrPs were incorporated by intestinal epitheliocytes in the follicle-associated epithelium and villi within 1 hour. PrP-positive cells accumulated in the subfollicle region of Peyer's patches a few hours thereafter. PrP-positive cells spread toward the mesenteric lymph nodes and spleen after the accumulation of PrPs in the Peyer's patches. The number of PrP molecules in the mesenteric lymph nodes and spleen peaked at 2 days and 6 days after inoculation, respectively. The epitheliocytes in the follicle-associated epithelium incorporating PrPs were annexin V-positive microfold cells and PrP-positive cells in Peyer's patches and spleen were CD11b-positive and CD14-positive macrophages. Additionally, PrP-positive cells in Peyer's patches and spleen were detected in the vicinity of peripheral nerve fibers in the early stages of infection. These results indicate that orally delivered PrPs were incorporated by microfold cells promptly after challenge and that macrophages might act as a transporter of incorporated PrPs from the Peyer's patches to other lymphoid tissues and the peripheral nervous system."},"publication_date":"2011-07-18","publication_name":{"en":"The American Journal of Pathology","ja":"The American Journal of Pathology"},"volume":"Vol.179","number":"No.3","starting_page":"1301","ending_page":"1309","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.ajpath.2011.05.058"],"issn":["1525-2191"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:32, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21516351","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=239741","label":"url"}],"paper_title":{"en":"Effects of a Brain-Engraftable Microglial Cell Line Expressing Anti-Prion scFv Antibodies on Survival Times of Mice Infected with Scrapie Prions.","ja":"Effects of a Brain-Engraftable Microglial Cell Line Expressing Anti-Prion scFv Antibodies on Survival Times of Mice Infected with Scrapie Prions."},"authors":{"en":[{"name":"Fujita Koji"},{"name":"Yamaguchi Yoshitaka"},{"name":"Mori Tsuyoshi"},{"name":"Muramatsu Naomi"},{"name":"Miyamoto Takahito"},{"name":"Yano Masashi"},{"name":"Miyata Hironori"},{"name":"Ootsuyama Akira"},{"name":"Sawada Makoto"},{"name":"Matsuda Haruo"},{"name":"Kaji Ryuji"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"藤田 浩司"},{"name":"Yamaguchi Yoshitaka"},{"name":"森 剛志"},{"name":"Muramatsu Naomi"},{"name":"Miyamoto Takahito"},{"name":"矢野 雅司"},{"name":"Miyata Hironori"},{"name":"Ootsuyama Akira"},{"name":"Sawada Makoto"},{"name":"Matsuda Haruo"},{"name":"梶 龍兒"},{"name":"坂口 末廣"}]},"description":{"en":"We first verified that a single chain Fv fragment against prion protein (anti-PrP scFv) was secreted by HEK293T cells and prevented prion replication in infected cells. We then stably expressed anti-PrP scFv in brain-engraftable murine microglial cells and intracerebrally injected these cells into mice before or after infection with prions. Interestingly, the injection before or at an early time point after infection attenuated the infection marginally but significantly prolonged survival times of the mice. These suggest that the ex vivo gene transfer of anti-PrP scFvs using brain-engraftable cells could be a possible immunotherapeutic approach against prion diseases.","ja":"We first verified that a single chain Fv fragment against prion protein (anti-PrP scFv) was secreted by HEK293T cells and prevented prion replication in infected cells. We then stably expressed anti-PrP scFv in brain-engraftable murine microglial cells and intracerebrally injected these cells into mice before or after infection with prions. Interestingly, the injection before or at an early time point after infection attenuated the infection marginally but significantly prolonged survival times of the mice. These suggest that the ex vivo gene transfer of anti-PrP scFvs using brain-engraftable cells could be a possible immunotherapeutic approach against prion diseases."},"publication_date":"2011-04-23","publication_name":{"en":"Cellular and Molecular Neurobiology","ja":"Cellular and Molecular Neurobiology"},"volume":"Vol.31","number":"No.7","starting_page":"999","ending_page":"1008","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s10571-011-9696-z"],"issn":["1573-6830"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:33, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/19514955","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=213673","label":"url"}],"paper_title":{"en":"Antibody-based immunotherapeutic attempts experimental animal models of prion diseases.","ja":"Antibody-based immunotherapeutic attempts experimental animal models of prion diseases."},"authors":{"en":[{"name":"Sakaguchi Suehiro"},{"name":"Ishibashi Daisuke"},{"name":"Matsuda Haruo"}],"ja":[{"name":"坂口 末廣"},{"name":"Ishibashi Daisuke"},{"name":"Matsuda Haruo"}]},"description":{"en":"There has been a dramatic decrease in the risk of transmission of bovine spongiform encephalopathy to humans. In contrast, the risk of human-to-human transmission of variant Creutzfeldt-Jakob disease (vCJD) via medical treatments became potentially high since 4 vCJD cases were reported to be possibly transmitted through blood transfusion in the UK. However, no treatments are yet available for curing prion diseases. Conversion of the normal prion protein, PrP(C), to the amyloidogenic PrP, PrP(Sc), plays a pivotal role in the pathogenesis. Recently, certain anti-PrP or anti-37/67-kDa laminin receptor (LRP/LR) antibodies were shown to have the potential to cure chronically infected cells, clearing PrP(Sc) from the cells. This has raised the possibility of antibody based-immunotherapy for prion diseases. This article aims to introduce and discuss the recently published attempts of immunotherapy in prion diseases. Bibliographic research was carried out using the PubMed database. Patent literature was searched using the UK Intellectual Property Office website. No satisfying consequences in animals could be detected with anti-PrP antibodies directly infused into the brains of animals by the intraventricular route or by anti-PrP or anti-LRP/LR single chain fragment antibodies directly delivered into the brain by virus vector-mediated gene transfer. This is probably because such delivery systems failed to deliver the antibodies to the neurons relevant for the treatments.","ja":"There has been a dramatic decrease in the risk of transmission of bovine spongiform encephalopathy to humans. In contrast, the risk of human-to-human transmission of variant Creutzfeldt-Jakob disease (vCJD) via medical treatments became potentially high since 4 vCJD cases were reported to be possibly transmitted through blood transfusion in the UK. However, no treatments are yet available for curing prion diseases. Conversion of the normal prion protein, PrP(C), to the amyloidogenic PrP, PrP(Sc), plays a pivotal role in the pathogenesis. Recently, certain anti-PrP or anti-37/67-kDa laminin receptor (LRP/LR) antibodies were shown to have the potential to cure chronically infected cells, clearing PrP(Sc) from the cells. This has raised the possibility of antibody based-immunotherapy for prion diseases. This article aims to introduce and discuss the recently published attempts of immunotherapy in prion diseases. Bibliographic research was carried out using the PubMed database. Patent literature was searched using the UK Intellectual Property Office website. No satisfying consequences in animals could be detected with anti-PrP antibodies directly infused into the brains of animals by the intraventricular route or by anti-PrP or anti-LRP/LR single chain fragment antibodies directly delivered into the brain by virus vector-mediated gene transfer. This is probably because such delivery systems failed to deliver the antibodies to the neurons relevant for the treatments."},"publication_date":"2009-07-01","publication_name":{"en":"Expert Opinion on Therapeutic Patents","ja":"Expert Opinion on Therapeutic Patents"},"volume":"Vol.19","number":"No.7","starting_page":"907","ending_page":"917","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1517/13543770902988530"],"issn":["1744-7674"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:34, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/19275739","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=213672","label":"url"}],"paper_title":{"en":"Prospects for Preventative Vaccines against Prion Diseases","ja":"Prospects for Preventative Vaccines against Prion Diseases"},"authors":{"en":[{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"坂口 末廣"}]},"description":{"en":"Emergence of variant type of Creutzfeldt-Jakob disease (vCJD) in humans due to infection from bovine spongiform encephalopathy contaminated beef and recent reports of human-to-human transmission of vCJD via blood transfusion have raised great concern about an epidemic of vCJD. The disease is currently difficult to diagnose during pre-clinical stages and requires a very long incubation period for neurological symptoms to be evident. This therefore suggests that the disease is already latently spreading and that opportunity for infection is thus growing among human populations. Interestingly, passive immunization with antibodies against prion protein (PrP), a major component of the prion infectious agents, was shown to protect mice from infection, indicating the possibility of prion vaccines. However, PrP is a host protein therefore immune tolerance to PrP has hampered development of them. Here, the so far reported attempts to overcome the tolerance to elicit protective immunity to prions are briefly reviewed.","ja":"Emergence of variant type of Creutzfeldt-Jakob disease (vCJD) in humans due to infection from bovine spongiform encephalopathy contaminated beef and recent reports of human-to-human transmission of vCJD via blood transfusion have raised great concern about an epidemic of vCJD. The disease is currently difficult to diagnose during pre-clinical stages and requires a very long incubation period for neurological symptoms to be evident. This therefore suggests that the disease is already latently spreading and that opportunity for infection is thus growing among human populations. Interestingly, passive immunization with antibodies against prion protein (PrP), a major component of the prion infectious agents, was shown to protect mice from infection, indicating the possibility of prion vaccines. However, PrP is a host protein therefore immune tolerance to PrP has hampered development of them. Here, the so far reported attempts to overcome the tolerance to elicit protective immunity to prions are briefly reviewed."},"publication_date":"2009","publication_name":{"en":"Protein and Peptide Letters","ja":"Protein and Peptide Letters"},"volume":"Vol.16","number":"No.3","starting_page":"260","ending_page":"270","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2174/092986609787601804"],"issn":["0929-8665"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:35, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/18562311","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=187236","label":"url"}],"paper_title":{"en":"Dominant-negative effects of the N-terminal half of prion protein on neurotoxicity of prion protein-like protein/doppel in mice.","ja":"Dominant-negative effects of the N-terminal half of prion protein on neurotoxicity of prion protein-like protein/doppel in mice."},"authors":{"en":[{"name":"Yoshikawa Daisuke"},{"name":"Yamaguchi Naohiro"},{"name":"Ishibashi Daisuke"},{"name":"Yamanaka Hitoki"},{"name":"Okimura Nobuhiko"},{"name":"Yamaguti Yoshitaka"},{"name":"Mori Tsuyoshi"},{"name":"Miyata Hironori"},{"name":"Shigematsu Kazuto"},{"name":"Katamine Shigeru"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"Yoshikawa Daisuke"},{"name":"Yamaguchi Naohiro"},{"name":"Ishibashi Daisuke"},{"name":"Yamanaka Hitoki"},{"name":"Okimura Nobuhiko"},{"name":"山口 仁孝"},{"name":"森 剛志"},{"name":"Miyata Hironori"},{"name":"Shigematsu Kazuto"},{"name":"Katamine Shigeru"},{"name":"坂口 末廣"}]},"description":{"en":"Prion protein-like protein/doppel is neurotoxic, causing ataxia and Purkinje cell degeneration in mice, whereas prion protein antagonizes doppel-induced neurodegeneration. Doppel is homologous to the C-terminal half of prion protein but lacks the amino acid sequences corresponding to the N-terminal half of prion protein. We show here that transgenic mice expressing a fusion protein consisting of the N-terminal half, corresponding to residues 1-124, of prion protein and doppel in neurons failed to develop any neurological signs for up to 730 days in a background devoid of prion protein. In addition, the fusion protein prolonged the onset of ataxia in mice expressing exogenous doppel. These results suggested that the N-terminal part of prion protein has a neuroprotective potential acting both cis and trans on doppel. We also show that prion protein lacking the pre-octapeptide repeat (Delta25-50) or octapeptide repeat (Delta51-90) region alone could not impair the antagonistic function against doppel.","ja":"Prion protein-like protein/doppel is neurotoxic, causing ataxia and Purkinje cell degeneration in mice, whereas prion protein antagonizes doppel-induced neurodegeneration. Doppel is homologous to the C-terminal half of prion protein but lacks the amino acid sequences corresponding to the N-terminal half of prion protein. We show here that transgenic mice expressing a fusion protein consisting of the N-terminal half, corresponding to residues 1-124, of prion protein and doppel in neurons failed to develop any neurological signs for up to 730 days in a background devoid of prion protein. In addition, the fusion protein prolonged the onset of ataxia in mice expressing exogenous doppel. These results suggested that the N-terminal part of prion protein has a neuroprotective potential acting both cis and trans on doppel. We also show that prion protein lacking the pre-octapeptide repeat (Delta25-50) or octapeptide repeat (Delta51-90) region alone could not impair the antagonistic function against doppel."},"publication_date":"2008-08-29","publication_name":{"en":"The Journal of Biological Chemistry","ja":"The Journal of Biological Chemistry"},"volume":"Vol.283","number":"No.35","starting_page":"24202","ending_page":"24211","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1074/jbc.M804212200"],"issn":["0021-9258"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:36, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/19158506","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=187417","label":"url"}],"paper_title":{"en":"Antagonistic roles of the N-terminal domain of prion protein to doppel","ja":"Antagonistic roles of the N-terminal domain of prion protein to doppel"},"authors":{"en":[{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"坂口 末廣"}]},"description":{"en":"Prion protein (PrP)-like molecule, doppel (Dpl), is neurotoxic in mice, causing Purkinje cell degeneration. In contrast, PrP antagonizes Dpl in trans, rescuing mice from Purkinje cell death. We have previously shown that PrP with deletion of the N-terminal residues 23-88 failed to neutralize Dpl in mice, indicating that the N-terminal region, particularly that including residues 23-88, may have trans-protective activity against Dpl. Interestingly, PrP with deletion elongated to residues 121 or 134 in the N-terminal region was shown to be similarly neurotoxic to Dpl, indicating that the PrP C-terminal region may have toxicity which is normally prevented by the N-terminal domain in cis. We recently investigated further roles for the N-terminal region of PrP in antagonistic interactions with Dpl by producing three different types of transgenic mice. These mice expressed PrP with deletion of residues 25-50 or 51-90, or a fusion protein of the N-terminal region of PrP with Dpl. Here, we discuss a possible model for the antagonistic interaction between PrP and Dpl.","ja":"Prion protein (PrP)-like molecule, doppel (Dpl), is neurotoxic in mice, causing Purkinje cell degeneration. In contrast, PrP antagonizes Dpl in trans, rescuing mice from Purkinje cell death. We have previously shown that PrP with deletion of the N-terminal residues 23-88 failed to neutralize Dpl in mice, indicating that the N-terminal region, particularly that including residues 23-88, may have trans-protective activity against Dpl. Interestingly, PrP with deletion elongated to residues 121 or 134 in the N-terminal region was shown to be similarly neurotoxic to Dpl, indicating that the PrP C-terminal region may have toxicity which is normally prevented by the N-terminal domain in cis. We recently investigated further roles for the N-terminal region of PrP in antagonistic interactions with Dpl by producing three different types of transgenic mice. These mice expressed PrP with deletion of residues 25-50 or 51-90, or a fusion protein of the N-terminal region of PrP with Dpl. Here, we discuss a possible model for the antagonistic interaction between PrP and Dpl."},"publication_date":"2008-07-14","publication_name":{"en":"Prion","ja":"Prion"},"volume":"Vol.2","number":"No.3","starting_page":"107","ending_page":"111","languages":["eng"],"referee":true,"identifiers":{"doi":["10.4161/pri.2.3.7436"],"issn":["1933-690X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:37, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/18408883","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=187416","label":"url"}],"paper_title":{"en":"Cellular prion protein prevents brain damage after encephalomyocarditis virus infection in mice","ja":"Cellular prion protein prevents brain damage after encephalomyocarditis virus infection in mice"},"authors":{"en":[{"name":"Nasu-Nishimura Y"},{"name":"Taniuchi Y"},{"name":"Nishimura T"},{"name":"Sakudo A"},{"name":"Nakajima K"},{"name":"Ano Y"},{"name":"Sugiura K"},{"name":"Sakaguchi Suehiro"},{"name":"Itohara S"},{"name":"Onodera T"}],"ja":[{"name":"Nasu-Nishimura Y"},{"name":"Taniuchi Y"},{"name":"Nishimura T"},{"name":"Sakudo A"},{"name":"Nakajima K"},{"name":"Ano Y"},{"name":"Sugiura K"},{"name":"坂口 末廣"},{"name":"Itohara S"},{"name":"Onodera T"}]},"description":{"en":"Cellular prion protein (PrP(C)), a cell-surface glycoprotein normally associated with neurons, is also expressed in other cell types such as glia and lymphocytes. To further elucidate these roles of PrP(C), wild-type prion protein gene (Prnp(+/+)) mice and Prnp-deficient (Prnp(-/-)) mice were infected with encephalomyocarditis virus B variant (EMCV-B) via an intracranial route. EMCV-B causes encephalitis and apoptotic cell death in vivo. Histopathological studies revealed that Prnp(+/+) mice infected with 600 pfu of EMCV-B showed more severe infiltration of inflammatory cells, accompanied by higher activation of microglia cells around the hippocampus, than Prnp(-/-) mice; viz., no differences in the brain virus titer between these two lines of mice. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP, nick end-labeling (TUNEL) staining of the brain specimens revealed that the CA1 hippocampal pyramidal cells showed a larger number of apoptotic neurons in Prnp(-/-) than Prnp(+/+) mice. Based on all these findings, PrP(C) may play certain roles in the induction of inflammation and inhibition of apoptosis in vivo.","ja":"Cellular prion protein (PrP(C)), a cell-surface glycoprotein normally associated with neurons, is also expressed in other cell types such as glia and lymphocytes. To further elucidate these roles of PrP(C), wild-type prion protein gene (Prnp(+/+)) mice and Prnp-deficient (Prnp(-/-)) mice were infected with encephalomyocarditis virus B variant (EMCV-B) via an intracranial route. EMCV-B causes encephalitis and apoptotic cell death in vivo. Histopathological studies revealed that Prnp(+/+) mice infected with 600 pfu of EMCV-B showed more severe infiltration of inflammatory cells, accompanied by higher activation of microglia cells around the hippocampus, than Prnp(-/-) mice; viz., no differences in the brain virus titer between these two lines of mice. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP, nick end-labeling (TUNEL) staining of the brain specimens revealed that the CA1 hippocampal pyramidal cells showed a larger number of apoptotic neurons in Prnp(-/-) than Prnp(+/+) mice. Based on all these findings, PrP(C) may play certain roles in the induction of inflammation and inhibition of apoptosis in vivo."},"publication_date":"2008-04-12","publication_name":{"en":"Archives of Virology","ja":"Archives of Virology"},"volume":"Vol.153","number":"No.6","starting_page":"1007","ending_page":"1012","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s00705-008-0086-x"],"issn":["0304-8608"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:38, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=187418","label":"url"}],"paper_title":{"en":"Recent developments in therapeutics for prion diseases","ja":"Recent developments in therapeutics for prion diseases"},"authors":{"en":[{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"坂口 末廣"}]},"publication_date":"2008-01","publication_name":{"en":"Expert Opinion on Therapeutic Patents","ja":"Expert Opinion on Therapeutic Patents"},"volume":"Vol.18","number":"No.1","starting_page":"35","ending_page":"59","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1517/13543776.18.1.35"],"issn":["1354-3776"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:39, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/111516","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/17878669","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=171919","label":"url"}],"paper_title":{"en":"Molecular biology of prion protein and its first homologous protein","ja":"Molecular biology of prion protein and its first homologous protein"},"authors":{"en":[{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"坂口 末廣"}]},"description":{"en":"Conformational conversion of the normal cellular isoform of prion protein, PrP(C), a glycoprotein anchored to the cell membrane by a glycosylphosphatidylinositol moiety, into the abnormally folded, amyloidogenic prion protein, PrP(Sc), plays a pivotal role in the pathogenesis of prion diseases. It has been suggested that PrP(C) might be functionally disturbed by constitutive conversion to PrP(Sc) due to either the resulting depletion of PrP(C) or the dominant negative effects of PrP(Sc) on PrP(C) or both. Consistent with this, we and others showed that mice devoid of PrP(C) (PrP-/-) spontaneously developed abnormal phenotypes very similar to the neurological abnormalities of prion diseases, supporting the concept that functional loss of PrP(C) might at least be partly involved in the pathogenesis of the diseases. However, no neuronal cell death could be detected in PrP-/- mice, indicating that the functional loss of PrP(C) alone might not be enough to induce neuronal cell death, one of major pathological hallmarks of prion diseases. Interestingly, it was recently shown that the first identified PrP-like protein, termed PrPLP/Doppel (Dpl), is neurotoxic in the absence of PrP(C), causing Purkinje cell degeneration in the cerebellum of mice. Although it is not understood if PrP(Sc) could have a neurotoxic potential similar to PrPLP/Dpl, it is very interesting to speculate that accumulation of PrP(Sc) and the functional disturbance of PrP(C), both of which are caused by constitutive conversion, might be required for the neurodegeneration in prion diseases.","ja":"Conformational conversion of the normal cellular isoform of prion protein, PrP(C), a glycoprotein anchored to the cell membrane by a glycosylphosphatidylinositol moiety, into the abnormally folded, amyloidogenic prion protein, PrP(Sc), plays a pivotal role in the pathogenesis of prion diseases. It has been suggested that PrP(C) might be functionally disturbed by constitutive conversion to PrP(Sc) due to either the resulting depletion of PrP(C) or the dominant negative effects of PrP(Sc) on PrP(C) or both. Consistent with this, we and others showed that mice devoid of PrP(C) (PrP-/-) spontaneously developed abnormal phenotypes very similar to the neurological abnormalities of prion diseases, supporting the concept that functional loss of PrP(C) might at least be partly involved in the pathogenesis of the diseases. However, no neuronal cell death could be detected in PrP-/- mice, indicating that the functional loss of PrP(C) alone might not be enough to induce neuronal cell death, one of major pathological hallmarks of prion diseases. Interestingly, it was recently shown that the first identified PrP-like protein, termed PrPLP/Doppel (Dpl), is neurotoxic in the absence of PrP(C), causing Purkinje cell degeneration in the cerebellum of mice. Although it is not understood if PrP(Sc) could have a neurotoxic potential similar to PrPLP/Dpl, it is very interesting to speculate that accumulation of PrP(Sc) and the functional disturbance of PrP(C), both of which are caused by constitutive conversion, might be required for the neurodegeneration in prion diseases."},"publication_date":"2007-08","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"Vol.54","number":"No.3-4","starting_page":"211","ending_page":"223","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2152/jmi.54.211"],"issn":["1343-1420"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:40, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/17611634","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-35448993375&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=171918","label":"url"}],"paper_title":{"en":"Late-onset olfactory deficits and mitral cell loss in mice lacking prion protein with ectopic expression of Doppel","ja":"Late-onset olfactory deficits and mitral cell loss in mice lacking prion protein with ectopic expression of Doppel"},"authors":{"en":[{"name":"Kim CK"},{"name":"Sakudo A"},{"name":"Taniuchi Y"},{"name":"Shigematsu K"},{"name":"Kang CB"},{"name":"Saeki K"},{"name":"Matsumoto Y"},{"name":"Sakaguchi Suehiro"},{"name":"Itohara S"},{"name":"Onodera T"}],"ja":[{"name":"Kim CK"},{"name":"Sakudo A"},{"name":"Taniuchi Y"},{"name":"Shigematsu K"},{"name":"Kang CB"},{"name":"Saeki K"},{"name":"Matsumoto Y"},{"name":"坂口 末廣"},{"name":"Itohara S"},{"name":"Onodera T"}]},"description":{"en":"Several lines of prion protein gene (Prnp)-knockout mice such as ZrchI, ZrchII, Npu, Ngsk and Rcm0 have been generated. Of these, ZrchII, Ngsk and Rcm0 exhibit late-onset ataxia due to ectopic expression of Doppel (Dpl); a result of damage to the splicing acceptor of Prnp exon 3. Recently, we developed another line of Prnp-/- mice (Rikn), which was generated by gene targeting with more nucleotides by replacing intron 2 with the pgk-neo gene (cf. Ngsk Prnp-/- mice) and showed not only ataxia but also a lower olfactory sensitivity than the other Prnp-/- mouse line ZrchI at over 60 weeks of age. The histopathology of the elderly Rikn Prnp-/- mice showed mitral cell loss concomitantly observed with gliosis of astrocytes. Western blot analysis showed that Dpl was detected in the cerebrum, cerebellum and olfactory bulb of Rikn Prnp-/- mice, where aberrant histopathology was observed. Thus, mitral cell loss and gliosis induced by ectopic Dpl expression were probably associated with the late-onset olfactory deficits in Rikn Prnp-/- mice.","ja":"Several lines of prion protein gene (Prnp)-knockout mice such as ZrchI, ZrchII, Npu, Ngsk and Rcm0 have been generated. Of these, ZrchII, Ngsk and Rcm0 exhibit late-onset ataxia due to ectopic expression of Doppel (Dpl); a result of damage to the splicing acceptor of Prnp exon 3. Recently, we developed another line of Prnp-/- mice (Rikn), which was generated by gene targeting with more nucleotides by replacing intron 2 with the pgk-neo gene (cf. Ngsk Prnp-/- mice) and showed not only ataxia but also a lower olfactory sensitivity than the other Prnp-/- mouse line ZrchI at over 60 weeks of age. The histopathology of the elderly Rikn Prnp-/- mice showed mitral cell loss concomitantly observed with gliosis of astrocytes. Western blot analysis showed that Dpl was detected in the cerebrum, cerebellum and olfactory bulb of Rikn Prnp-/- mice, where aberrant histopathology was observed. Thus, mitral cell loss and gliosis induced by ectopic Dpl expression were probably associated with the late-onset olfactory deficits in Rikn Prnp-/- mice."},"publication_date":"2007-08","publication_name":{"en":"International Journal of Molecular Medicine","ja":"International Journal of Molecular Medicine"},"volume":"Vol.20","number":"No.2","starting_page":"169","ending_page":"176","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3892/ijmm.20.2.169"],"issn":["1107-3756"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:41, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/17498663","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=171917","label":"url"}],"paper_title":{"en":"Reduced response of splenocytes after mitogen-stimulation in the prion protein (PrP) gene-deficient mouse: PrPLP/Doppel production and cerebral degeneration","ja":"Reduced response of splenocytes after mitogen-stimulation in the prion protein (PrP) gene-deficient mouse: PrPLP/Doppel production and cerebral degeneration"},"authors":{"en":[{"name":"Kim CK"},{"name":"Hirose Y"},{"name":"Sakudo A"},{"name":"Takeyama N"},{"name":"Kang CB"},{"name":"Taniuchi Y"},{"name":"Matsumoto Y"},{"name":"Itohara S"},{"name":"Sakaguchi Suehiro"},{"name":"Onodera T"}],"ja":[{"name":"Kim CK"},{"name":"Hirose Y"},{"name":"Sakudo A"},{"name":"Takeyama N"},{"name":"Kang CB"},{"name":"Taniuchi Y"},{"name":"Matsumoto Y"},{"name":"Itohara S"},{"name":"坂口 末廣"},{"name":"Onodera T"}]},"description":{"en":"Splenocytes of wild-type (Prnp(+/+)) and prion protein gene-deficient (Prnp(-/-)) mice were treated with various activation stimuli such as T cell mitogen concanavalin A (ConA), phorbol 12-myristate 13-acetate (PMA)+ionomycin (Io), or B cell mitogen lipopolysaccharide (LPS). Cellular prion protein (PrP(C)) expression was enhanced following ConA stimulation, but not PMA+Io or LPS in Prnp(+/+) splenocytes. Rikn Prnp(-/-) splenocytes elicited lower cell proliferations than Prnp(+/+) or Zrch I Prnp(-/-) splenocytes after LPS stimulation and showed sporadic nerve cells in the cerebral cortex and deeper structure. Around the degenerated nerve cells, mild vacuolation in the neuropil was observed. This neural alteration correlated well to the suppressed response of B cells in the spleen. The finding that discrete lesions within the central nervous systems induced marked modulation of immune function probably indicates the existence of a delicately balanced neural-endocrine network by PrP(C) and PrPLP/Doppel.","ja":"Splenocytes of wild-type (Prnp(+/+)) and prion protein gene-deficient (Prnp(-/-)) mice were treated with various activation stimuli such as T cell mitogen concanavalin A (ConA), phorbol 12-myristate 13-acetate (PMA)+ionomycin (Io), or B cell mitogen lipopolysaccharide (LPS). Cellular prion protein (PrP(C)) expression was enhanced following ConA stimulation, but not PMA+Io or LPS in Prnp(+/+) splenocytes. Rikn Prnp(-/-) splenocytes elicited lower cell proliferations than Prnp(+/+) or Zrch I Prnp(-/-) splenocytes after LPS stimulation and showed sporadic nerve cells in the cerebral cortex and deeper structure. Around the degenerated nerve cells, mild vacuolation in the neuropil was observed. This neural alteration correlated well to the suppressed response of B cells in the spleen. The finding that discrete lesions within the central nervous systems induced marked modulation of immune function probably indicates the existence of a delicately balanced neural-endocrine network by PrP(C) and PrPLP/Doppel."},"publication_date":"2007-08","publication_name":{"en":"Biochemical and Biophysical Research Communications","ja":"Biochemical and Biophysical Research Communications"},"volume":"Vol.358","number":"No.2","starting_page":"469","ending_page":"474","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bbrc.2007.04.174"],"issn":["0006-291X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:42, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/17569776","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=171916","label":"url"}],"paper_title":{"en":"Doppel induces degeneration of cerebellar Purkinje cells independently of Bax","ja":"Doppel induces degeneration of cerebellar Purkinje cells independently of Bax"},"authors":{"en":[{"name":"Dong Jiaxin"},{"name":"Li Aimin"},{"name":"Yamaguchi Naohiro"},{"name":"Sakaguchi Suehiro"},{"name":"Harris A. David"}],"ja":[{"name":"Dong Jiaxin"},{"name":"Li Aimin"},{"name":"Yamaguchi Naohiro"},{"name":"坂口 末廣"},{"name":"Harris A. David"}]},"description":{"en":"Doppel (Dpl) is a prion protein paralog that causes neurodegeneration when expressed ectopically in the brain. To investigate the cellular mechanism underlying this effect, we analyzed Dpl-expressing transgenic mice in which the gene for the proapoptotic protein Bax had been deleted. We found that Bax deletion does not alter either clinical symptoms or Purkinje cell degeneration in Dpl transgenic mice. In addition, we observed that degenerating Purkinje cells in these animals do not display DNA fragmentation or caspase-3 activation. Our results suggest that non-Bax-dependent pathways mediate the toxic effects of Dpl in Purkinje cells, highlighting a possible role for nonapoptotic mechanisms in the death of these neurons.","ja":"Doppel (Dpl) is a prion protein paralog that causes neurodegeneration when expressed ectopically in the brain. To investigate the cellular mechanism underlying this effect, we analyzed Dpl-expressing transgenic mice in which the gene for the proapoptotic protein Bax had been deleted. We found that Bax deletion does not alter either clinical symptoms or Purkinje cell degeneration in Dpl transgenic mice. In addition, we observed that degenerating Purkinje cells in these animals do not display DNA fragmentation or caspase-3 activation. Our results suggest that non-Bax-dependent pathways mediate the toxic effects of Dpl in Purkinje cells, highlighting a possible role for nonapoptotic mechanisms in the death of these neurons."},"publication_date":"2007-08","publication_name":{"en":"The American Journal of Pathology","ja":"The American Journal of Pathology"},"volume":"Vol.171","number":"No.2","starting_page":"599","ending_page":"607","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2353/ajpath.2007.070262"],"issn":["0002-9440"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:43, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/17446686","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=171848","label":"url"}],"paper_title":{"en":"Serum withdrawal-induced apoptosis in ZrchI prion protein (PrP) gene-deficient neuronal cell line is suppressed by PrP, independent of Doppel","ja":"Serum withdrawal-induced apoptosis in ZrchI prion protein (PrP) gene-deficient neuronal cell line is suppressed by PrP, independent of Doppel"},"authors":{"en":[{"name":"Takuya Nishimura"},{"name":"Akikazu Sakudo"},{"name":"Yoriko Hashiyama"},{"name":"Akiko Yachi"},{"name":"Keiichi Saeki"},{"name":"Yoshitsugu Matsumoto"},{"name":"Masaharu Ogawa"},{"name":"Sakaguchi Suehiro"},{"name":"Shigeyoshi Itohara"},{"name":"Takashi Onodera"}],"ja":[{"name":"Takuya Nishimura"},{"name":"Akikazu Sakudo"},{"name":"Yoriko Hashiyama"},{"name":"Akiko Yachi"},{"name":"Keiichi Saeki"},{"name":"Yoshitsugu Matsumoto"},{"name":"Masaharu Ogawa"},{"name":"坂口 末廣"},{"name":"Shigeyoshi Itohara"},{"name":"Takashi Onodera"}]},"description":{"en":"Previous studies have shown that cellular prion protein (PrP(C)) plays anti-apoptotic and antioxidative role against cell death induced by serum-deprivation (SDP) in an immortalized prion protein gene-deficient neuronal cell line derived from Rikn prion protein (PrP) gene-deficient (Prnp(-/-)) mice, which ectopically produce excess Doppel (Dpl) (PrP-like glycoprotein). To investigate whether PrP(C) inhibits apoptotic neuronal cell death without Dpl, an immortalized cell line was established from the brain of ZrchI Prnp(-/-) mice, which do not show ectopic expression of Dpl. The results using a ZrchI neuronal Prnp(-/-) cell line (NpL2) showed that PrP(C) potently inhibited SDP-induced apoptotic cell death. Furthermore, PrP(C) expression enhanced the superoxide dismutase (SOD) activity in NpL2 cells. These results indicate that Dpl production did not affect anti-apoptotic and anti-oxidative functions of PrP, suggesting that PrP(C) may be directly correlated with protection against oxidative stress.","ja":"Previous studies have shown that cellular prion protein (PrP(C)) plays anti-apoptotic and antioxidative role against cell death induced by serum-deprivation (SDP) in an immortalized prion protein gene-deficient neuronal cell line derived from Rikn prion protein (PrP) gene-deficient (Prnp(-/-)) mice, which ectopically produce excess Doppel (Dpl) (PrP-like glycoprotein). To investigate whether PrP(C) inhibits apoptotic neuronal cell death without Dpl, an immortalized cell line was established from the brain of ZrchI Prnp(-/-) mice, which do not show ectopic expression of Dpl. The results using a ZrchI neuronal Prnp(-/-) cell line (NpL2) showed that PrP(C) potently inhibited SDP-induced apoptotic cell death. Furthermore, PrP(C) expression enhanced the superoxide dismutase (SOD) activity in NpL2 cells. These results indicate that Dpl production did not affect anti-apoptotic and anti-oxidative functions of PrP, suggesting that PrP(C) may be directly correlated with protection against oxidative stress."},"publication_date":"2007-04","publication_name":{"en":"Microbiology and Immunology","ja":"Microbiology and Immunology"},"volume":"Vol.51","number":"No.4","starting_page":"457","ending_page":"466","languages":["eng"],"referee":true,"identifiers":{"issn":["0385-5600"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:44, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/17165097","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=171799","label":"url"}],"paper_title":{"en":"Immunohistochemical characterization of cell types expressing the cellular prion protein in the small intestine of cattle and mice","ja":"Immunohistochemical characterization of cell types expressing the cellular prion protein in the small intestine of cattle and mice"},"authors":{"en":[{"name":"Miyazawa K"},{"name":"Kanaya T"},{"name":"Tanaka S"},{"name":"Takakura I"},{"name":"Watanabe K"},{"name":"Ohwada S"},{"name":"Kitazawa H"},{"name":"Rose MT"},{"name":"Sakaguchi Suehiro"},{"name":"Katamine S"},{"name":"Yamaguchi T"},{"name":"Aso H"}],"ja":[{"name":"Miyazawa K"},{"name":"Kanaya T"},{"name":"Tanaka S"},{"name":"Takakura I"},{"name":"Watanabe K"},{"name":"Ohwada S"},{"name":"Kitazawa H"},{"name":"Rose MT"},{"name":"坂口 末廣"},{"name":"Katamine S"},{"name":"Yamaguchi T"},{"name":"Aso H"}]},"description":{"en":"The gastrointestinal tract is thought to be the main site of entry for the pathological isoform of the prion protein (PrP(Sc)). Prion diseases are believed to result from a conformational change of the cellular prion protein (PrP(c)) to PrP(Sc). Therefore, PrP(c) expression is a prerequisite for the infection and spread of the disease to the central nervous system. However, the distribution of PrP(c) in the gut is still a matter of controversy. We therefore investigated the localization of PrP(c) in the bovine and murine small intestine. In cattle, most PrP(c) positive epithelial cells were detected in the duodenum, while a few positive cells were found in the jejunum. PrP(c) was expressed in serotonin producing cells. In bovine Peyer's patches, PrP(c) was distributed in extrafollicular areas, but not in the germinal centre of the jejunum and ileum. PrP(c) was expressed in myeloid lineage cells such as myeloid dendritic cells and macrophages. In mice, PrP(c) was expressed in some epithelial cells throughout the small intestine as well as in cells such as follicular dendritic cell in the germinal centre of Peyer's patches. In this study, we demonstrate that there are a number of differences in the localization of PrP(c) between the murine and bovine small intestines.","ja":"The gastrointestinal tract is thought to be the main site of entry for the pathological isoform of the prion protein (PrP(Sc)). Prion diseases are believed to result from a conformational change of the cellular prion protein (PrP(c)) to PrP(Sc). Therefore, PrP(c) expression is a prerequisite for the infection and spread of the disease to the central nervous system. However, the distribution of PrP(c) in the gut is still a matter of controversy. We therefore investigated the localization of PrP(c) in the bovine and murine small intestine. In cattle, most PrP(c) positive epithelial cells were detected in the duodenum, while a few positive cells were found in the jejunum. PrP(c) was expressed in serotonin producing cells. In bovine Peyer's patches, PrP(c) was distributed in extrafollicular areas, but not in the germinal centre of the jejunum and ileum. PrP(c) was expressed in myeloid lineage cells such as myeloid dendritic cells and macrophages. In mice, PrP(c) was expressed in some epithelial cells throughout the small intestine as well as in cells such as follicular dendritic cell in the germinal centre of Peyer's patches. In this study, we demonstrate that there are a number of differences in the localization of PrP(c) between the murine and bovine small intestines."},"publication_date":"2007-03","publication_name":{"en":"Histochemistry and Cell Biology","ja":"Histochemistry and Cell Biology"},"volume":"Vol.127","number":"No.3","starting_page":"291","ending_page":"301","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s00418-006-0250-x"],"issn":["0948-6143"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:45, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/17280480","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=171798","label":"url"}],"paper_title":{"en":"Recent developments in mucosal vaccines against prion diseases","ja":"Recent developments in mucosal vaccines against prion diseases"},"authors":{"en":[{"name":"Sakaguchi Suehiro"},{"name":"Takeshi Arakawa"}],"ja":[{"name":"坂口 末廣"},{"name":"Takeshi Arakawa"}]},"description":{"en":"Bovine spongiform encephalopathy in cattle is highly suspected to be orally transmitted to humans through contaminated food, causing new variant Creutzfeldt-Jakob disease. However, no prophylactic procedures against these diseases, such as vaccines, in particular those stimulating mucosal protective immunity, have been established. The causative agents of these diseases, termed prions, consist of the host-encoded prion protein (PrP). Therefore, prions are immunologically tolerated, inducing no host antibody responses. This immune tolerance to PrP has hampered the development of vaccines against prions. We and others recently reported that the immune tolerance could be successfully broken and mucosal immunity could be stimulated by mucosal immunization of mice with PrP fused with bacterial enterotoxin or delivered using an attenuated Salmonella strain, eliciting significantly higher immunoglobulin A and G antibody responses against PrP. In this review, we will discuss these reports.","ja":"Bovine spongiform encephalopathy in cattle is highly suspected to be orally transmitted to humans through contaminated food, causing new variant Creutzfeldt-Jakob disease. However, no prophylactic procedures against these diseases, such as vaccines, in particular those stimulating mucosal protective immunity, have been established. The causative agents of these diseases, termed prions, consist of the host-encoded prion protein (PrP). Therefore, prions are immunologically tolerated, inducing no host antibody responses. This immune tolerance to PrP has hampered the development of vaccines against prions. We and others recently reported that the immune tolerance could be successfully broken and mucosal immunity could be stimulated by mucosal immunization of mice with PrP fused with bacterial enterotoxin or delivered using an attenuated Salmonella strain, eliciting significantly higher immunoglobulin A and G antibody responses against PrP. In this review, we will discuss these reports."},"publication_date":"2007-02","publication_name":{"en":"Expert Review of Vaccines","ja":"Expert Review of Vaccines"},"volume":"Vol.6","number":"No.1","starting_page":"75","ending_page":"85","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1586/14760584.6.1.75"],"issn":["1744-8395"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:46, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/17055125","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=171797","label":"url"}],"paper_title":{"en":"Immunization with recombinant bovine but not mouse prion protein delays the onset of disease in mice inoculated with a mouse-adapted prion","ja":"Immunization with recombinant bovine but not mouse prion protein delays the onset of disease in mice inoculated with a mouse-adapted prion"},"authors":{"en":[{"name":"Ishibashi Daisuke"},{"name":"Yamanaka Hitoki"},{"name":"Yamaguchi Naohiro"},{"name":"Yoshikawa Daisuke"},{"name":"Nakamura Risa"},{"name":"Okimura Nobuhiko"},{"name":"Yamaguti Yoshitaka"},{"name":"Shigematsu Kazuto"},{"name":"Katamine Shigeru"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"Ishibashi Daisuke"},{"name":"Yamanaka Hitoki"},{"name":"Yamaguchi Naohiro"},{"name":"Yoshikawa Daisuke"},{"name":"Nakamura Risa"},{"name":"Okimura Nobuhiko"},{"name":"山口 仁孝"},{"name":"Shigematsu Kazuto"},{"name":"Katamine Shigeru"},{"name":"坂口 末廣"}]},"description":{"en":"Host tolerance to endogenous prion protein (PrP) has hampered the development of prion vaccines as PrP is a major component of prions. Indeed, we show that immunization of mice with mouse recombinant PrP elicited no prophylactic effect against a mouse-adapted prion. However, interestingly, mice immunized with recombinant bovine PrP developed the disease significantly later than non-immunized mice after inoculation of a mouse prion. Sheep recombinant PrP exhibited variable prophylactic effects. Mouse recombinant PrP stimulated only very weak antibody responses. In contrast, bovine recombinant PrP was higher immunogenic and produced variable amounts of anti-mouse PrP autoantibodies. Sheep recombinant PrP was also immunogenic but produced more variable amounts of anti-PrP autoantibodies. These results might open a new way for development of prion vaccines.","ja":"Host tolerance to endogenous prion protein (PrP) has hampered the development of prion vaccines as PrP is a major component of prions. Indeed, we show that immunization of mice with mouse recombinant PrP elicited no prophylactic effect against a mouse-adapted prion. However, interestingly, mice immunized with recombinant bovine PrP developed the disease significantly later than non-immunized mice after inoculation of a mouse prion. Sheep recombinant PrP exhibited variable prophylactic effects. Mouse recombinant PrP stimulated only very weak antibody responses. In contrast, bovine recombinant PrP was higher immunogenic and produced variable amounts of anti-mouse PrP autoantibodies. Sheep recombinant PrP was also immunogenic but produced more variable amounts of anti-PrP autoantibodies. These results might open a new way for development of prion vaccines."},"publication_date":"2007-01","publication_name":{"en":"Vaccine","ja":"Vaccine"},"volume":"Vol.25","number":"No.6","starting_page":"985","ending_page":"992","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.vaccine.2006.09.078"],"issn":["0264-410X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:47, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/17034959","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=171792","label":"url"}],"paper_title":{"en":"Newly established in vitro system with fluorescent proteins shows that abnormal expression of downstream prion protein-like protein in mice is probably due to functional disconnection between splicing and 3' formation of prion protein pre-mRNA","ja":"Newly established in vitro system with fluorescent proteins shows that abnormal expression of downstream prion protein-like protein in mice is probably due to functional disconnection between splicing and 3' formation of prion protein pre-mRNA"},"authors":{"en":[{"name":"Daisuke Yoshikawa"},{"name":"Juraj Kopacek"},{"name":"Naohiro Yamaguchi"},{"name":"Daisuke Ishibashi"},{"name":"Hitoki Yamanaka"},{"name":"Yamaguti Yoshitaka"},{"name":"Shigeru Katamine"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"Daisuke Yoshikawa"},{"name":"Juraj Kopacek"},{"name":"Naohiro Yamaguchi"},{"name":"Daisuke Ishibashi"},{"name":"Hitoki Yamanaka"},{"name":"山口 仁孝"},{"name":"Shigeru Katamine"},{"name":"坂口 末廣"}]},"description":{"en":"We and others previously showed that, in some lines of prion protein (PrP)-knockout mice, the downstream PrP-like protein (PrPLP/Dpl) was abnormally expressed in brains partly due to impaired cleavage/polyadenylation of the residual PrP promoter-driven pre-mRNA despite the presence of a poly(A) signal. In this study, we newly established an in vitro transient transfection system in which abnormal expression of PrPLP/Dpl can be visualized by expression of the green fluorescence protein, EGFP, in cultured cells. No EGFP was detected in cells transfected by a vector carrying a PrP genomic fragment including the region targeted in the knockout mice intact upstream of the PrPLP/Dpl gene. In contrast, deletion of the targeted region from the vector caused expression of EGFP. By employing this system with other vectors carrying various deletions or point mutations in the targeted region, we identified that disruption of the splicing elements in the PrP terminal intron caused the expression of EGFP. Recent lines of evidence indicate that terminal intron splicing and cleavage/polyadenylation of pre-mRNA are functionally linked to each other. Taken together, our newly established system shows that the abnormal expression of PrPLP/Dpl in PrP-knockout mice caused by the impaired cleavage/polyadenylation of the PrP promoter-driven pre-mRNA is due to the functional dissociation between the pre-mRNA machineries, in particular those of cleavage/polyadenylation and splicing. Our newly established in vitro system, in which the functional dissociation between the pre-mRNA machineries can be visualized by EGFP green fluorescence, may be useful for studies of the functional connection of pre-mRNA machineries.","ja":"We and others previously showed that, in some lines of prion protein (PrP)-knockout mice, the downstream PrP-like protein (PrPLP/Dpl) was abnormally expressed in brains partly due to impaired cleavage/polyadenylation of the residual PrP promoter-driven pre-mRNA despite the presence of a poly(A) signal. In this study, we newly established an in vitro transient transfection system in which abnormal expression of PrPLP/Dpl can be visualized by expression of the green fluorescence protein, EGFP, in cultured cells. No EGFP was detected in cells transfected by a vector carrying a PrP genomic fragment including the region targeted in the knockout mice intact upstream of the PrPLP/Dpl gene. In contrast, deletion of the targeted region from the vector caused expression of EGFP. By employing this system with other vectors carrying various deletions or point mutations in the targeted region, we identified that disruption of the splicing elements in the PrP terminal intron caused the expression of EGFP. Recent lines of evidence indicate that terminal intron splicing and cleavage/polyadenylation of pre-mRNA are functionally linked to each other. Taken together, our newly established system shows that the abnormal expression of PrPLP/Dpl in PrP-knockout mice caused by the impaired cleavage/polyadenylation of the PrP promoter-driven pre-mRNA is due to the functional dissociation between the pre-mRNA machineries, in particular those of cleavage/polyadenylation and splicing. Our newly established in vitro system, in which the functional dissociation between the pre-mRNA machineries can be visualized by EGFP green fluorescence, may be useful for studies of the functional connection of pre-mRNA machineries."},"publication_date":"2007-01","publication_name":{"en":"Gene","ja":"Gene"},"volume":"Vol.386","number":"No.1-2","starting_page":"139","ending_page":"146","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.gene.2006.08.028"],"issn":["0378-1119"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:48, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/16651721","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143125","label":"url"}],"paper_title":{"en":"Surface plasmon resonance analysis for the screening of ant-prion compounds.","ja":"Surface plasmon resonance analysis for the screening of ant-prion compounds."},"authors":{"en":[{"name":"Kawatake Satoshi"},{"name":"Nishimura Yuki"},{"name":"Sakaguchi Suehiro"},{"name":"Iwaki Toru"},{"name":"Doh-ura Katsumi"}],"ja":[{"name":"Kawatake Satoshi"},{"name":"Nishimura Yuki"},{"name":"坂口 末廣"},{"name":"Iwaki Toru"},{"name":"Doh-ura Katsumi"}]},"description":{"en":"The interaction of anti-prion compounds and amyloid binding dyes with a carboxy-terminal domain of prion protein (PrP121-231) was examined using surface plasmon resonance (SPR) and compared with inhibition activities of abnormal PrP formation in scrapie-infected cells. Most examined compounds had affinities for PrP121-231: antimalarials had low affinities, whereas Congo red, phthalocyanine and thioflavin S had high affinities. The SPR binding response correlated with the inhibition activity of abnormal PrP formation. Several drugs were screened using SPR to verify the findings: propranolol was identified as a new anti-prion compound. This fact indicates that drug screenings by this assay are useful.","ja":"The interaction of anti-prion compounds and amyloid binding dyes with a carboxy-terminal domain of prion protein (PrP121-231) was examined using surface plasmon resonance (SPR) and compared with inhibition activities of abnormal PrP formation in scrapie-infected cells. Most examined compounds had affinities for PrP121-231: antimalarials had low affinities, whereas Congo red, phthalocyanine and thioflavin S had high affinities. The SPR binding response correlated with the inhibition activity of abnormal PrP formation. Several drugs were screened using SPR to verify the findings: propranolol was identified as a new anti-prion compound. This fact indicates that drug screenings by this assay are useful."},"publication_date":"2006-05-29","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"Vol.29","number":"No.5","starting_page":"927","ending_page":"932","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.29.927"],"issn":["0918-6158"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:49, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/16446015","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143140","label":"url"}],"paper_title":{"en":"Enhanced mucosal immunogenicity of prion protein following fusion with B subunit of Escherichia coli heat-labile enterotoxin.","ja":"Enhanced mucosal immunogenicity of prion protein following fusion with B subunit of Escherichia coli heat-labile enterotoxin."},"authors":{"en":[{"name":"Yamanaka Hitoki"},{"name":"Ishibashi Daisuke"},{"name":"Yamaguchi Naohiro"},{"name":"Yoshikawa Daisuke"},{"name":"Nakamura Risa"},{"name":"Okimura Nobuhiko"},{"name":"Arakawa Takeshi"},{"name":"Tsuji Takao"},{"name":"Katamine Shigeru"},{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"Yamanaka Hitoki"},{"name":"Ishibashi Daisuke"},{"name":"Yamaguchi Naohiro"},{"name":"Yoshikawa Daisuke"},{"name":"Nakamura Risa"},{"name":"Okimura Nobuhiko"},{"name":"Arakawa Takeshi"},{"name":"Tsuji Takao"},{"name":"Katamine Shigeru"},{"name":"坂口 末廣"}]},"description":{"en":"Mucosal vaccine against prion protein (PrP), a major component of prions, is urgently awaited since the oral transmission of prions from cattle to humans is highly suspected. In the present study, we produced recombinant bovine and mouse PrPs fused with or without the B subunit of Escherichia coli heat-labile enterotoxin (LTB) and intranasally immunized mice with these fused proteins. Fusion with LTB markedly enhanced the mucosal immunogenicity of bovine PrP, producing a marked increase in specific IgG and IgA titer in serum. Mouse PrP also showed slightly increased immunogenicity following fusion with LTB. These results demonstrate that LTB-fused PrPs might be potential candidates for protective mucosal prion vaccines.","ja":"Mucosal vaccine against prion protein (PrP), a major component of prions, is urgently awaited since the oral transmission of prions from cattle to humans is highly suspected. In the present study, we produced recombinant bovine and mouse PrPs fused with or without the B subunit of Escherichia coli heat-labile enterotoxin (LTB) and intranasally immunized mice with these fused proteins. Fusion with LTB markedly enhanced the mucosal immunogenicity of bovine PrP, producing a marked increase in specific IgG and IgA titer in serum. Mouse PrP also showed slightly increased immunogenicity following fusion with LTB. These results demonstrate that LTB-fused PrPs might be potential candidates for protective mucosal prion vaccines."},"publication_date":"2006-04-05","publication_name":{"en":"Vaccine","ja":"Vaccine"},"volume":"Vol.24","number":"No.15","starting_page":"2815","ending_page":"2823","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.vaccine.2005.12.054"],"issn":["0264-410X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:50, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/16198494","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143141","label":"url"}],"paper_title":{"en":"Female-specific neuroprotection against transient brain ischemia observed in mice devoid of prion protein is abolished by ectopic expression of prion protein-like protein.","ja":"Female-specific neuroprotection against transient brain ischemia observed in mice devoid of prion protein is abolished by ectopic expression of prion protein-like protein."},"authors":{"en":[{"name":"Sakurai-Yamashita Yasuko"},{"name":"Sakaguchi Suehiro"},{"name":"Yoshikawa Daisuke"},{"name":"Okimura Nobuhiko"},{"name":"Masuda Yoshiko"},{"name":"Katamine Shigeru"},{"name":"Niwa Masami"}],"ja":[{"name":"Sakurai-Yamashita Yasuko"},{"name":"坂口 末廣"},{"name":"Yoshikawa Daisuke"},{"name":"Okimura Nobuhiko"},{"name":"Masuda Yoshiko"},{"name":"Katamine Shigeru"},{"name":"Niwa Masami"}]},"description":{"en":"This study was designed to examine the function of cellular prion protein and prion protein-like protein/Doppel, in transient ischemia-related neuronal death in the hippocampus. Two different lines of mice devoid of cellular prion protein, Zrch I Prnp(0/0) and Ngsk Prnp(0/0), were used. The former lacks cellular prion protein whereas the latter ectopically expresses prion protein-like protein/Doppel in the brain in the absence of cellular prion protein. Mice were subjected to 10 min-occlusion of the bilateral common carotid arteries with recovery for 14 days. Less than 10% of the pyramidal neurons in the CA1 subfield were degenerated in male and female wild-type mice. In contrast, more than half of the neurons were lost in male Zrch I Prnp(0/0) and Ngsk Prnp(0/0) mice. Such severe neuronal loss was also observed in female Ngsk Prnp(0/0) mice. However, female Zrch I Prnp(0/0) mice showed mild neuronal loss similar to wild-type mice. Flunarizine, a T- and L-type Ca(2+)-channel antagonist, significantly reduced the neuronal loss in female but not in male Ngsk Prnp(0/0) mice. These results indicate that loss of cellular prion protein renders hippocampal neurons susceptible to ischemic insult specifically in male but not female mice and the ectopic expression of prion protein-like protein/Doppel aggravates the ischemic neuronal death in female prion protein-null mice probably via overloading of Ca(2+)-dependent signaling.","ja":"This study was designed to examine the function of cellular prion protein and prion protein-like protein/Doppel, in transient ischemia-related neuronal death in the hippocampus. Two different lines of mice devoid of cellular prion protein, Zrch I Prnp(0/0) and Ngsk Prnp(0/0), were used. The former lacks cellular prion protein whereas the latter ectopically expresses prion protein-like protein/Doppel in the brain in the absence of cellular prion protein. Mice were subjected to 10 min-occlusion of the bilateral common carotid arteries with recovery for 14 days. Less than 10% of the pyramidal neurons in the CA1 subfield were degenerated in male and female wild-type mice. In contrast, more than half of the neurons were lost in male Zrch I Prnp(0/0) and Ngsk Prnp(0/0) mice. Such severe neuronal loss was also observed in female Ngsk Prnp(0/0) mice. However, female Zrch I Prnp(0/0) mice showed mild neuronal loss similar to wild-type mice. Flunarizine, a T- and L-type Ca(2+)-channel antagonist, significantly reduced the neuronal loss in female but not in male Ngsk Prnp(0/0) mice. These results indicate that loss of cellular prion protein renders hippocampal neurons susceptible to ischemic insult specifically in male but not female mice and the ectopic expression of prion protein-like protein/Doppel aggravates the ischemic neuronal death in female prion protein-null mice probably via overloading of Ca(2+)-dependent signaling."},"publication_date":"2005-09-28","publication_name":{"en":"Neuroscience","ja":"Neuroscience"},"volume":"Vol.136","number":"No.1","starting_page":"281","ending_page":"287","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.neuroscience.2005.06.095"],"issn":["0306-4522"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:51, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15890950","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143144","label":"url"}],"paper_title":{"en":"Biological and biochemical characteristics of prion strains conserved in persistently-infected cell cultures.","ja":"Biological and biochemical characteristics of prion strains conserved in persistently-infected cell cultures."},"authors":{"en":[{"name":"Arima Kazuhiko"},{"name":"Nishida Noriyuki"},{"name":"Sakaguchi Suehiro"},{"name":"Shigematsu Kazuto"},{"name":"Atarashi Ryuichiro"},{"name":"Yamaguchi Naohiro"},{"name":"Yoshikawa Daisuke"},{"name":"Yoon Jaewoo"},{"name":"Watanabe Ken"},{"name":"Kobayashi Nobuyuki"},{"name":"Mouillet-Richard Sophie"},{"name":"Lehmann Sylvain"},{"name":"Katamine Shigeru"}],"ja":[{"name":"Arima Kazuhiko"},{"name":"Nishida Noriyuki"},{"name":"坂口 末廣"},{"name":"Shigematsu Kazuto"},{"name":"Atarashi Ryuichiro"},{"name":"Yamaguchi Naohiro"},{"name":"Yoshikawa Daisuke"},{"name":"Yoon Jaewoo"},{"name":"Watanabe Ken"},{"name":"Kobayashi Nobuyuki"},{"name":"Mouillet-Richard Sophie"},{"name":"Lehmann Sylvain"},{"name":"Katamine Shigeru"}]},"description":{"en":"Abnormal prion protein (PrP(Sc)) plays a central role in the transmission of prion diseases, but the molecular basis of prion strains with distinct biological characteristics remains to be elucidated. We analyzed the characteristics of prion disease by using mice inoculated with the Chandler and Fukuoka-1 strains propagated in a cultured mouse neuronal cell line, GT1-7, which is highly permissive to replication of the infectious agents. Strain-specific biological characteristics, including clinical manifestations, incubation period as related to the infectious unit, and pathological profiles, remained unchanged after passages in the cell cultures. We noted some differences in the biochemical aspects of PrP(Sc) between brain tissues and GT1-7 cells which were unlikely to affect the strain phenotypes. On the other hand, the proteinase K-resistant PrP core fragments derived from Fukuoka-1-infected tissues and cells were slightly larger than those from Chandler-infected versions. Moreover, Fukuoka-1 infection, but not Chandler infection, gave an extra fragment with a low molecular weight, approximately 13 kDa, in both brain tissues and GT1-7 cells. This cell culture model persistently infected with different strains will provide a new insight into the understanding of the molecular basis of prion diversity.","ja":"Abnormal prion protein (PrP(Sc)) plays a central role in the transmission of prion diseases, but the molecular basis of prion strains with distinct biological characteristics remains to be elucidated. We analyzed the characteristics of prion disease by using mice inoculated with the Chandler and Fukuoka-1 strains propagated in a cultured mouse neuronal cell line, GT1-7, which is highly permissive to replication of the infectious agents. Strain-specific biological characteristics, including clinical manifestations, incubation period as related to the infectious unit, and pathological profiles, remained unchanged after passages in the cell cultures. We noted some differences in the biochemical aspects of PrP(Sc) between brain tissues and GT1-7 cells which were unlikely to affect the strain phenotypes. On the other hand, the proteinase K-resistant PrP core fragments derived from Fukuoka-1-infected tissues and cells were slightly larger than those from Chandler-infected versions. Moreover, Fukuoka-1 infection, but not Chandler infection, gave an extra fragment with a low molecular weight, approximately 13 kDa, in both brain tissues and GT1-7 cells. This cell culture model persistently infected with different strains will provide a new insight into the understanding of the molecular basis of prion diversity."},"publication_date":"2005-06","publication_name":{"en":"Journal of Virology","ja":"Journal of Virology"},"volume":"Vol.79","number":"No.11","starting_page":"7104","ending_page":"7112","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1128/JVI.79.11.7104-7112.2005"],"issn":["0022-538X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:52, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-58149471049&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143143","label":"url"}],"paper_title":{"en":"Prion protein, prion protein-like protein, and neurodegeneration.","ja":"Prion protein, prion protein-like protein, and neurodegeneration."},"authors":{"en":[{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"坂口 末廣"}]},"publication_date":"2005","publication_name":{"en":"Neurodegeneration and Prion Disease edited by David R. Brown","ja":"Neurodegeneration and Prion Disease edited by David R. Brown"},"starting_page":"167","ending_page":"193","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/0-387-23923-5_7"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:53, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15351724","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143150","label":"url"}],"paper_title":{"en":"Cellular prion protein regulates intracellular hydrogen peroxide level and prevents copper-induced apoptosis.","ja":"Cellular prion protein regulates intracellular hydrogen peroxide level and prevents copper-induced apoptosis."},"authors":{"en":[{"name":"Nishimura Takuya"},{"name":"Sakudo Akikazu"},{"name":"Nakamura Izuru"},{"name":"Lee Deug-chan"},{"name":"Taniuchi Yoichiro"},{"name":"Saeki Keiichi"},{"name":"Matsumoto Yoshitsugu"},{"name":"Ogawa Masaharu"},{"name":"Sakaguchi Suehiro"},{"name":"Itohara Shigeyoshi"},{"name":"Onodera Takashi"}],"ja":[{"name":"Nishimura Takuya"},{"name":"Sakudo Akikazu"},{"name":"Nakamura Izuru"},{"name":"Lee Deug-chan"},{"name":"Taniuchi Yoichiro"},{"name":"Saeki Keiichi"},{"name":"Matsumoto Yoshitsugu"},{"name":"Ogawa Masaharu"},{"name":"坂口 末廣"},{"name":"Itohara Shigeyoshi"},{"name":"Onodera Takashi"}]},"description":{"en":"The function of cellular prion protein (PrPC), which is a copper binding protein, remains unclear. To elucidate the mechanisms in which PrPC is involved in neuroprotection, we compared death signals in prion protein gene-deficient (Prnp-/-) primary cerebellar granular neurons (CGNs) to those with wild-type (WT) CGNs. When copper was exposed to these CGNs, ZrchI, and Rikn Prnp-/- CGNs were more sensitized and underwent apoptotic cell death more readily than WT CGNs. Furthermore, the level of intracellular hydrogen peroxide (H2O2) in WT CGNs increased by copper toxicity, whereas those in ZrchI and Rikn Prnp-/- CGNs did not. These results suggest that PrPC modulates the intracellular H2O2 level as a copper-binding protein to protect CGNs from apoptotic cell death possibly due to inhibiting a Fenton reaction.","ja":"The function of cellular prion protein (PrPC), which is a copper binding protein, remains unclear. To elucidate the mechanisms in which PrPC is involved in neuroprotection, we compared death signals in prion protein gene-deficient (Prnp-/-) primary cerebellar granular neurons (CGNs) to those with wild-type (WT) CGNs. When copper was exposed to these CGNs, ZrchI, and Rikn Prnp-/- CGNs were more sensitized and underwent apoptotic cell death more readily than WT CGNs. Furthermore, the level of intracellular hydrogen peroxide (H2O2) in WT CGNs increased by copper toxicity, whereas those in ZrchI and Rikn Prnp-/- CGNs did not. These results suggest that PrPC modulates the intracellular H2O2 level as a copper-binding protein to protect CGNs from apoptotic cell death possibly due to inhibiting a Fenton reaction."},"publication_date":"2004-10-08","publication_name":{"en":"Biochemical and Biophysical Research Communications","ja":"Biochemical and Biophysical Research Communications"},"volume":"Vol.323","number":"No.1","starting_page":"218","ending_page":"222","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bbrc.2004.08.087"],"issn":["0006-291X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:54, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/30017808163/","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15194501","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1360011145119574272/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143151","label":"url"}],"paper_title":{"en":"Doppel-induced Purkinje cell death is stoichiometrically abrogated by prion protein.","ja":"Doppel-induced Purkinje cell death is stoichiometrically abrogated by prion protein."},"authors":{"en":[{"name":"Yamaguchi Naohiro"},{"name":"Sakaguchi Suehiro"},{"name":"Shigematsu Kazuto"},{"name":"Okimura Nobuhiko"},{"name":"Katamine Shigeru"}],"ja":[{"name":"Yamaguchi Naohiro"},{"name":"坂口 末廣"},{"name":"Shigematsu Kazuto"},{"name":"Okimura Nobuhiko"},{"name":"Katamine Shigeru"}]},"description":{"en":"Mice devoid of prion protein (PrP) exhibiting ataxia and Purkinje cell degeneration, such as Ngsk Prnp(-/-) mice, ectopically express PrP-like protein, Dpl, in neurons including Purkinje cells. In this study, two types of transgenic (tg) mice expressing Dpl in neurons, tg(N-Dpl), or Purkinje cells only, tg(P-Dpl), were generated on the background of non-ataxic Zrch I Prnp(-/-) mice. In contrast to the tg mice with the Prnp(+/+) background, both tg mice with the Prnp(-/-) alleles developed Purkinje cell degeneration after incubation periods inversely correlated to the levels of Dpl. Some tg mice hemizygous for Prnp allele also developed disease but much later than those carrying the Prnp(-/-) alleles. This indicates that Dpl expressed by Purkinje cells itself is toxic to the cells, and that the neurotoxicity is stoichiometrically antagonized by PrP.","ja":"Mice devoid of prion protein (PrP) exhibiting ataxia and Purkinje cell degeneration, such as Ngsk Prnp(-/-) mice, ectopically express PrP-like protein, Dpl, in neurons including Purkinje cells. In this study, two types of transgenic (tg) mice expressing Dpl in neurons, tg(N-Dpl), or Purkinje cells only, tg(P-Dpl), were generated on the background of non-ataxic Zrch I Prnp(-/-) mice. In contrast to the tg mice with the Prnp(+/+) background, both tg mice with the Prnp(-/-) alleles developed Purkinje cell degeneration after incubation periods inversely correlated to the levels of Dpl. Some tg mice hemizygous for Prnp allele also developed disease but much later than those carrying the Prnp(-/-) alleles. This indicates that Dpl expressed by Purkinje cells itself is toxic to the cells, and that the neurotoxicity is stoichiometrically antagonized by PrP."},"publication_date":"2004-07-09","publication_name":{"en":"Biochemical and Biophysical Research Communications","ja":"Biochemical and Biophysical Research Communications"},"volume":"Vol.319","number":"No.4","starting_page":"1247","ending_page":"1252","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bbrc.2004.05.115"],"issn":["0006-291X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:55, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/14706620","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143153","label":"url"}],"paper_title":{"en":"Prion protein suppresses perturbation of cellular copper homeostasis under oxidative conditions.","ja":"Prion protein suppresses perturbation of cellular copper homeostasis under oxidative conditions."},"authors":{"en":[{"name":"Sakudo Akikazu"},{"name":"Lee Deug-chan"},{"name":"Yoshimura Etsuro"},{"name":"Nagasaka Seiji"},{"name":"Nitta Kayako"},{"name":"Saeki Keiichi"},{"name":"Matsumoto Yoshitsugu"},{"name":"Lehmann Sylvain"},{"name":"Itohara Shigeyoshi"},{"name":"Sakaguchi Suehiro"},{"name":"Onodera Takashi"}],"ja":[{"name":"Sakudo Akikazu"},{"name":"Lee Deug-chan"},{"name":"Yoshimura Etsuro"},{"name":"Nagasaka Seiji"},{"name":"Nitta Kayako"},{"name":"Saeki Keiichi"},{"name":"Matsumoto Yoshitsugu"},{"name":"Lehmann Sylvain"},{"name":"Itohara Shigeyoshi"},{"name":"坂口 末廣"},{"name":"Onodera Takashi"}]},"description":{"en":"Prion protein (PrP) binds copper and exhibits superoxide dismutase-like activity, while the roles of PrP in copper homeostasis remain controversial. Using Zeeman graphite furnace atomic absorption spectroscopy, we quantified copper levels in immortalized PrP gene (Prnp)-deficient neuronal cells transfected with Prnp and/or Prnd, which encodes PrP-like protein (PrPLP/Dpl), in the presence or absence of oxidative stress induced by serum deprivation. In the presence of serum, copper levels were not significantly affected by the expression of PrP and/or PrPLP/Dpl, whereas serum deprivation induced a decrease in copper levels that was inhibited by PrP but not by PrPLP/Dpl. The inhibitory effect of PrP on the decrease of copper levels was prevented by overexpression of PrPLP/Dpl. These findings indicate that PrP specifically stabilizes copper homeostasis, which is perturbed under oxidative conditions, while PrPLP/Dpl overexpression prevents PrP function in copper homeostasis, suggesting an interaction of PrP and PrPLP/Dpl and distinct functions between PrP and PrPLP/Dpl on metal homeostasis. Taken together, these results strongly suggest that PrP, in addition to its antioxidant properties, plays a role in stabilizing cellular copper homeostasis under oxidative conditions.","ja":"Prion protein (PrP) binds copper and exhibits superoxide dismutase-like activity, while the roles of PrP in copper homeostasis remain controversial. Using Zeeman graphite furnace atomic absorption spectroscopy, we quantified copper levels in immortalized PrP gene (Prnp)-deficient neuronal cells transfected with Prnp and/or Prnd, which encodes PrP-like protein (PrPLP/Dpl), in the presence or absence of oxidative stress induced by serum deprivation. In the presence of serum, copper levels were not significantly affected by the expression of PrP and/or PrPLP/Dpl, whereas serum deprivation induced a decrease in copper levels that was inhibited by PrP but not by PrPLP/Dpl. The inhibitory effect of PrP on the decrease of copper levels was prevented by overexpression of PrPLP/Dpl. These findings indicate that PrP specifically stabilizes copper homeostasis, which is perturbed under oxidative conditions, while PrPLP/Dpl overexpression prevents PrP function in copper homeostasis, suggesting an interaction of PrP and PrPLP/Dpl and distinct functions between PrP and PrPLP/Dpl on metal homeostasis. Taken together, these results strongly suggest that PrP, in addition to its antioxidant properties, plays a role in stabilizing cellular copper homeostasis under oxidative conditions."},"publication_date":"2004-01-23","publication_name":{"en":"Biochemical and Biophysical Research Communications","ja":"Biochemical and Biophysical Research Communications"},"volume":"Vol.313","number":"No.4","starting_page":"850","ending_page":"855","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bbrc.2003.12.020"],"issn":["0006-291X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:56, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143147","label":"url"}],"paper_title":{"en":"Antagonistic roles of prion protein and prion protein-like protein in neurodegeneration.","ja":"Antagonistic roles of prion protein and prion protein-like protein in neurodegeneration."},"authors":{"en":[{"name":"Sakaguchi Suehiro"}],"ja":[{"name":"坂口 末廣"}]},"publication_date":"2004","publication_name":{"en":"Recent Research Developments in Experimental Medicine","ja":"Recent Research Developments in Experimental Medicine"},"volume":"Vol.1","starting_page":"47","ending_page":"61","languages":["eng"],"referee":true,"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:57, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143145","label":"url"}],"paper_title":{"en":"The absence of prion-like infectivity in mice expressing prion protein-like protein.","ja":"The absence of prion-like infectivity in mice expressing prion protein-like protein."},"authors":{"en":[{"name":"Atarashi Ryuichiro"},{"name":"Sakaguchi Suehiro"},{"name":"Shigematsu Kazuto"},{"name":"Katamine Shigeru"}],"ja":[{"name":"Atarashi Ryuichiro"},{"name":"坂口 末廣"},{"name":"Shigematsu Kazuto"},{"name":"Katamine Shigeru"}]},"publication_date":"2004","publication_name":{"en":"EXCLI Journal","ja":"EXCLI Journal"},"volume":"Vol.3","starting_page":"82","ending_page":"90","languages":["eng"],"referee":true,"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:58, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/12847134","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143156","label":"url"}],"paper_title":{"en":"Cellular prion protein promotes Brucella infection into macrophages.","ja":"Cellular prion protein promotes Brucella infection into macrophages."},"authors":{"en":[{"name":"Watarai Masahisa"},{"name":"Kim Suk"},{"name":"Erdenebaatar Janchivdorj"},{"name":"Makino Sou-ichi"},{"name":"Horiuchi Motohiro"},{"name":"Shirahata Toshikazu"},{"name":"Sakaguchi Suehiro"},{"name":"Katamine Shigeru"}],"ja":[{"name":"Watarai Masahisa"},{"name":"Kim Suk"},{"name":"Erdenebaatar Janchivdorj"},{"name":"Makino Sou-ichi"},{"name":"Horiuchi Motohiro"},{"name":"Shirahata Toshikazu"},{"name":"坂口 末廣"},{"name":"Katamine Shigeru"}]},"description":{"en":"The products of the Brucella abortus virB gene locus, which are highly similar to conjugative DNA transfer system, enable the bacterium to replicate within macrophage vacuoles. The replicative phagosome is thought to be established by the interaction of a substrate of the VirB complex with macrophages, although the substrate and its host cellular target have not yet been identified. We report here that Hsp60, a member of the GroEL family of chaperonins, of B. abortus is capable of interacting directly or indirectly with cellular prion protein (PrPC) on host cells. Aggregation of PrPC tail-like formation was observed during bacterial swimming internalization into macrophages and PrPC was selectively incorporated into macropinosomes containing B. abortus. Hsp60 reacted strongly with serum from human brucellosis patients and was exposed on the bacterial surface via a VirB complex-associated process. Under in vitro and in vivo conditions, Hsp60 of B. abortus bound to PrPC. Hsp60 of B. abortus, expressed on the surface of Lactococcus lactis, promoted the aggregation of PrPC but not PrPC tail formation on macrophages. The PrPC deficiency prevented swimming internalization and intracellular replication of B. abortus, with the result that phagosomes bearing the bacteria were targeted into the endocytic network. These results indicate that signal transduction induced by the interaction between bacterial Hsp60 and PrPC on macrophages contributes to the establishment of B. abortus infection.","ja":"The products of the Brucella abortus virB gene locus, which are highly similar to conjugative DNA transfer system, enable the bacterium to replicate within macrophage vacuoles. The replicative phagosome is thought to be established by the interaction of a substrate of the VirB complex with macrophages, although the substrate and its host cellular target have not yet been identified. We report here that Hsp60, a member of the GroEL family of chaperonins, of B. abortus is capable of interacting directly or indirectly with cellular prion protein (PrPC) on host cells. Aggregation of PrPC tail-like formation was observed during bacterial swimming internalization into macrophages and PrPC was selectively incorporated into macropinosomes containing B. abortus. Hsp60 reacted strongly with serum from human brucellosis patients and was exposed on the bacterial surface via a VirB complex-associated process. Under in vitro and in vivo conditions, Hsp60 of B. abortus bound to PrPC. Hsp60 of B. abortus, expressed on the surface of Lactococcus lactis, promoted the aggregation of PrPC but not PrPC tail formation on macrophages. The PrPC deficiency prevented swimming internalization and intracellular replication of B. abortus, with the result that phagosomes bearing the bacteria were targeted into the endocytic network. These results indicate that signal transduction induced by the interaction between bacterial Hsp60 and PrPC on macrophages contributes to the establishment of B. abortus infection."},"publication_date":"2003-07-07","publication_name":{"en":"The Journal of Experimental Medicine","ja":"The Journal of Experimental Medicine"},"volume":"Vol.198","number":"No.1","starting_page":"5","ending_page":"17","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1084/jem.20021980"],"issn":["0022-1007"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:59, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/12759361","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143158","label":"url"}],"paper_title":{"en":"Deletion of N-terminal residues 23-88 from prion protein (PrP) abrogates the potential to rescue PrP-deficient mice from PrP-like protein/Doppel-induced neurodegeneration.","ja":"Deletion of N-terminal residues 23-88 from prion protein (PrP) abrogates the potential to rescue PrP-deficient mice from PrP-like protein/Doppel-induced neurodegeneration."},"authors":{"en":[{"name":"Atarashi Ryuichiro"},{"name":"Nishida Noriyuki"},{"name":"Shigematsu Kazuto"},{"name":"Goto Shinji"},{"name":"Kondo Takahito"},{"name":"Sakaguchi Suehiro"},{"name":"Katamine Shigeru"}],"ja":[{"name":"Atarashi Ryuichiro"},{"name":"Nishida Noriyuki"},{"name":"Shigematsu Kazuto"},{"name":"Goto Shinji"},{"name":"Kondo Takahito"},{"name":"坂口 末廣"},{"name":"Katamine Shigeru"}]},"description":{"en":"Accumulating evidence has suggested that prion protein (PrP) is neuroprotective and that a PrP-like protein/Doppel (PrPLP/Dpl) is neurotoxic. A line of PrP-deficient mice, Ngsk Prnp0/0, ectopically expressing PrPLP/Dpl in neurons, exhibits late-onset ataxia because of Purkinje cell death that is prevented by a transgene encoding wild-type mouse PrP. To elucidate the mechanisms of neurodegeneration in these mice, we introduced five types of PrP transgene, namely one heterologous hamster, two mouse/hamster chimeric genes, and two mutants, each of which encoded PrP lacking residues 23-88 (MHM2.del23-88) or with E199K substitution (Mo.E199K), into Ngsk Prnp0/0 mice. Only MHM2.del23-88 failed to rescue the mice from the Purkinje cell death. The transgenic mice, MHM2.del23-88/Ngsk Prnp0/0, expressed several times more PrP than did wild-type (Prnp+/+) mice and PrPLP/Dpl at an equivalent level to Ngsk Prnp0/0 mice. Little difference was observed in the pathology and onset of ataxia between Ngsk Prnp0/0 and MHM2.del23-88/Ngsk Prnp0/0. No detergent-insoluble PrPLP/Dpl was detectable in the central nervous system of Ngsk Prnp0/0 mice even after the onset of ataxia. Our findings provide evidence that the N-terminal residues 23-88 of PrP containing the unique octapeptide-repeat region is crucial for preventing Purkinje cell death in Prnp0/0 mice expressing PrPLP/Dpl in the neuron.","ja":"Accumulating evidence has suggested that prion protein (PrP) is neuroprotective and that a PrP-like protein/Doppel (PrPLP/Dpl) is neurotoxic. A line of PrP-deficient mice, Ngsk Prnp0/0, ectopically expressing PrPLP/Dpl in neurons, exhibits late-onset ataxia because of Purkinje cell death that is prevented by a transgene encoding wild-type mouse PrP. To elucidate the mechanisms of neurodegeneration in these mice, we introduced five types of PrP transgene, namely one heterologous hamster, two mouse/hamster chimeric genes, and two mutants, each of which encoded PrP lacking residues 23-88 (MHM2.del23-88) or with E199K substitution (Mo.E199K), into Ngsk Prnp0/0 mice. Only MHM2.del23-88 failed to rescue the mice from the Purkinje cell death. The transgenic mice, MHM2.del23-88/Ngsk Prnp0/0, expressed several times more PrP than did wild-type (Prnp+/+) mice and PrPLP/Dpl at an equivalent level to Ngsk Prnp0/0 mice. Little difference was observed in the pathology and onset of ataxia between Ngsk Prnp0/0 and MHM2.del23-88/Ngsk Prnp0/0. No detergent-insoluble PrPLP/Dpl was detectable in the central nervous system of Ngsk Prnp0/0 mice even after the onset of ataxia. Our findings provide evidence that the N-terminal residues 23-88 of PrP containing the unique octapeptide-repeat region is crucial for preventing Purkinje cell death in Prnp0/0 mice expressing PrPLP/Dpl in the neuron."},"publication_date":"2003-05-19","publication_name":{"en":"The Journal of Biological Chemistry","ja":"The Journal of Biological Chemistry"},"volume":"Vol.278","number":"No.31","starting_page":"28944","ending_page":"28949","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1074/jbc.M303655200"],"issn":["0021-9258"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:60, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/11844868","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143167","label":"url"}],"paper_title":{"en":"Abnormal activation of glial cells in the brains of prion protein-deficient mice ectopically expressing prion protein-like protein, PrPLP/Dpl.","ja":"Abnormal activation of glial cells in the brains of prion protein-deficient mice ectopically expressing prion protein-like protein, PrPLP/Dpl."},"authors":{"en":[{"name":"Atarashi Ryuichiro"},{"name":"Sakaguchi Suehiro"},{"name":"Shigematsu Kazuto"},{"name":"Arima Kazuhiko"},{"name":"Okimura Nobuhiko"},{"name":"Yamaguchi Naohiro"},{"name":"Li A"},{"name":"Kopacek Juraj"},{"name":"Katamine Shigeru"}],"ja":[{"name":"Atarashi Ryuichiro"},{"name":"坂口 末廣"},{"name":"Shigematsu Kazuto"},{"name":"Arima Kazuhiko"},{"name":"Okimura Nobuhiko"},{"name":"Yamaguchi Naohiro"},{"name":"Li A"},{"name":"Kopacek Juraj"},{"name":"Katamine Shigeru"}]},"description":{"en":"Some lines of mice homozygous for a disrupted prion protein gene (Prnp), including Ngsk Prnp(0/0) mice, exhibit Purkinje cell degeneration as a consequence of the ectopic overexpression of the downstream gene for prion protein-like protein (PrPLP/Dpl) in the brain, but others, such as Zrch I Prnp(0/0) mice, show neither the neurodegeneration nor the expression of PrPLP/Dpl. In the present study, we found that Ngsk Prnp(0/0), but not Zrch I Prnp(0/0) mice, developed gliosis involving both astrocytes and microglia in the brain. The brains from wild-type (Prnp(+/+)), Ngsk Prnp(0/0), Zrch I Prnp(0/0), and reconstituted Ngsk Prnp(0/0) mice carrying a mouse PrP transgene, designated Tg(P) Ngsk Prnp(0/0) mice, were subjected into Northern blotting and in situ hybridization using probes of glial fibrillary acidic protein (GFAP) and lysozyme M (LM) specific for astrocytes and microglia, respectively. Immunohistochemistry was also performed on the brain sections using anti-GFAP and anti-F4/80 antibodies. Northern blotting demonstrated upregulated expression of the genes for GFAP and LM in the brains of Ngsk Prnp(0/0), but not in Zrch I Prnp(0/0) mice. A transgene for normal mouse PrP(C) successfully rescued Ngsk Prnp(0/0) mice from the glial activation. In situ hybridization and immunohistochemistry revealed activated astrocytes and microglia mainly in the white matter of both the forebrains and cerebella. In contrast, there was no evidence of neuronal injury except for the Purkinje cell degeneration. Moreover, the glial cell activation was notable well before the onset of the Purkinje cell degeneration. These findings strongly suggest that ectopic PrPLP/Dpl in the absence of PrP(C) is actively involved in the glial-cell activation in the brain.","ja":"Some lines of mice homozygous for a disrupted prion protein gene (Prnp), including Ngsk Prnp(0/0) mice, exhibit Purkinje cell degeneration as a consequence of the ectopic overexpression of the downstream gene for prion protein-like protein (PrPLP/Dpl) in the brain, but others, such as Zrch I Prnp(0/0) mice, show neither the neurodegeneration nor the expression of PrPLP/Dpl. In the present study, we found that Ngsk Prnp(0/0), but not Zrch I Prnp(0/0) mice, developed gliosis involving both astrocytes and microglia in the brain. The brains from wild-type (Prnp(+/+)), Ngsk Prnp(0/0), Zrch I Prnp(0/0), and reconstituted Ngsk Prnp(0/0) mice carrying a mouse PrP transgene, designated Tg(P) Ngsk Prnp(0/0) mice, were subjected into Northern blotting and in situ hybridization using probes of glial fibrillary acidic protein (GFAP) and lysozyme M (LM) specific for astrocytes and microglia, respectively. Immunohistochemistry was also performed on the brain sections using anti-GFAP and anti-F4/80 antibodies. Northern blotting demonstrated upregulated expression of the genes for GFAP and LM in the brains of Ngsk Prnp(0/0), but not in Zrch I Prnp(0/0) mice. A transgene for normal mouse PrP(C) successfully rescued Ngsk Prnp(0/0) mice from the glial activation. In situ hybridization and immunohistochemistry revealed activated astrocytes and microglia mainly in the white matter of both the forebrains and cerebella. In contrast, there was no evidence of neuronal injury except for the Purkinje cell degeneration. Moreover, the glial cell activation was notable well before the onset of the Purkinje cell degeneration. These findings strongly suggest that ectopic PrPLP/Dpl in the absence of PrP(C) is actively involved in the glial-cell activation in the brain."},"publication_date":"2001-12","publication_name":{"en":"Molecular Medicine","ja":"Molecular Medicine"},"volume":"Vol.7","number":"No.12","starting_page":"803","ending_page":"809","languages":["eng"],"referee":true,"identifiers":{"issn":["1076-1551"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:61, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/11714097","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143160","label":"url"}],"paper_title":{"en":"Similar target, different effects: late-onset ataxia and spatial learning in prion protein-deficient mouse lines.","ja":"Similar target, different effects: late-onset ataxia and spatial learning in prion protein-deficient mouse lines."},"authors":{"en":[{"name":"Valenti Paolo"},{"name":"Cozzio Antonio"},{"name":"Nishida Noriyuki"},{"name":"Wolfer P. David"},{"name":"Sakaguchi Suehiro"},{"name":"Lipp Hans-Peter"}],"ja":[{"name":"Valenti Paolo"},{"name":"Cozzio Antonio"},{"name":"Nishida Noriyuki"},{"name":"Wolfer P. David"},{"name":"坂口 末廣"},{"name":"Lipp Hans-Peter"}]},"description":{"en":"Several lines of mice with targeted deletion of the prion protein gene (Prnp) have been produced, some of them appearing phenotypically normal, others developing late-onset ataxia. This has been tentatively attributed to the size of the targeted deletion in the Prnp gene. but a masking role of genetic background could not be excluded. Thus, we have crossed an ataxic mutant line with large deletion of Prnp (Ngsk Prnp0/0) with a knockout line showing only partial deletion of Prnp and no neurological deficits (Zrchl Prnp0/0). A F2 generation was then studied for up to 70 weeks for co-segregation of lesion size and behavioral phenotype, including cognitive and neurological anomalies. These mice were later crossed with a recently generated PrP-deficient line also having a large deletion and late-onset ataxia (Zrch2 Prnp0/0). They underwent similar testing for up to 90 weeks. The ataxic phenotype always co-segregates with large homozygous deletions involving either the Ngsk or the Zrch2 allele, independent of genetic background or sex. Compound heterozygous Zrchl/Ngsk mice or Zrch1/Zrch2 mice showed intermediate neurological phenotypes, suggesting a gene-dosage effect of large deletions. At 12 weeks of age, large deletions were also associated with minor non-cognitive impairments in water maze learning, and hyperactivity in open field and elevated zero maze. These impairments were not predictive for the development of ataxia. Thus, the neurological deficits are closely associated with large deletions, which entail an upregulation of the recently discovered prion Doppel protein (Dpl), while genetic background factors seem to be responsible for shifting the onset of neurological symptoms.","ja":"Several lines of mice with targeted deletion of the prion protein gene (Prnp) have been produced, some of them appearing phenotypically normal, others developing late-onset ataxia. This has been tentatively attributed to the size of the targeted deletion in the Prnp gene. but a masking role of genetic background could not be excluded. Thus, we have crossed an ataxic mutant line with large deletion of Prnp (Ngsk Prnp0/0) with a knockout line showing only partial deletion of Prnp and no neurological deficits (Zrchl Prnp0/0). A F2 generation was then studied for up to 70 weeks for co-segregation of lesion size and behavioral phenotype, including cognitive and neurological anomalies. These mice were later crossed with a recently generated PrP-deficient line also having a large deletion and late-onset ataxia (Zrch2 Prnp0/0). They underwent similar testing for up to 90 weeks. The ataxic phenotype always co-segregates with large homozygous deletions involving either the Ngsk or the Zrch2 allele, independent of genetic background or sex. Compound heterozygous Zrchl/Ngsk mice or Zrch1/Zrch2 mice showed intermediate neurological phenotypes, suggesting a gene-dosage effect of large deletions. At 12 weeks of age, large deletions were also associated with minor non-cognitive impairments in water maze learning, and hyperactivity in open field and elevated zero maze. These impairments were not predictive for the development of ataxia. Thus, the neurological deficits are closely associated with large deletions, which entail an upregulation of the recently discovered prion Doppel protein (Dpl), while genetic background factors seem to be responsible for shifting the onset of neurological symptoms."},"publication_date":"2001-10","publication_name":{"en":"Neurogenetics","ja":"Neurogenetics"},"volume":"Vol.3","number":"No.4","starting_page":"173","ending_page":"184","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s100480100117"],"issn":["1364-6745"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:62, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/11100979","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-0033711734&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143193","label":"url"}],"paper_title":{"en":"Early appearance but lagged accumulation of detergent-insoluble prion protein in the brains of mice inoculated with a mouse-adapted Creutzfeldt-Jakob disease agent.","ja":"Early appearance but lagged accumulation of detergent-insoluble prion protein in the brains of mice inoculated with a mouse-adapted Creutzfeldt-Jakob disease agent."},"authors":{"en":[{"name":"Nakaoke Ryota"},{"name":"Sakaguchi Suehiro"},{"name":"Atarashi Ryuichiro"},{"name":"Nishida Noriuki"},{"name":"Arima Kazuhiko"},{"name":"Shigematsu Kazuto"},{"name":"Katamine Shigeru"}],"ja":[{"name":"Nakaoke Ryota"},{"name":"坂口 末廣"},{"name":"Atarashi Ryuichiro"},{"name":"Nishida Noriuki"},{"name":"Arima Kazuhiko"},{"name":"Shigematsu Kazuto"},{"name":"Katamine Shigeru"}]},"description":{"en":"1. To elucidate mechanisms for the generation of the detergent-insoluble, proteinase K-resistant prion protein (PrP(Sc)) from the detergent-soluble, proteinase K-sensitive PrP (PrP(C)) and the replication of the infectious agent in prion diseases, we followed the kinetics of detergent-insoluble PrP and PrP(Sc) levels, infectious titers, and associated pathological changes in the brains of mice inoculated with a mouse-adapted Creutzfeldt Jakob disease agent. 2. PrP(Sc) in brain homogenate and detergent-insoluble PrP enriched by two-cycle ultracentrifugation were detected by immunoblotting and their relative amounts were estimated according to a standard curve plotted between the amount of PrP and signal intensity on immunoblotting. The titer of infectivity was determined by the incubation periods of mice inoculated with the unfractionated homogenate on the basis of a standard curve plotted between the titer and incubation period. 3. Detergent-insoluble PrP became detectable 4 weeks postinoculation (p.i.) well before the detection of PrP(Sc). The low level of detergent-insoluble PrP continued until dramatic accumulation occurred at 14 weeks p.i., correlating well with the accumulation of PrP(Sc) and development of pathological changes. The infectious titer was undetectable at 4 weeks p.i. and its logarithmic increase occurred 10 weeks p.i. preceding the logarithmic accumulation of PrPs. 4. The lag time of detergent-insoluble PrP accumulation and the discrepancy between infectious titers and PrPs observed during the early period after inoculation suggest a slow and rate-limiting step for the detergent-insoluble PrP to become the infectious agent-associated PrP(Sc).","ja":"1. To elucidate mechanisms for the generation of the detergent-insoluble, proteinase K-resistant prion protein (PrP(Sc)) from the detergent-soluble, proteinase K-sensitive PrP (PrP(C)) and the replication of the infectious agent in prion diseases, we followed the kinetics of detergent-insoluble PrP and PrP(Sc) levels, infectious titers, and associated pathological changes in the brains of mice inoculated with a mouse-adapted Creutzfeldt Jakob disease agent. 2. PrP(Sc) in brain homogenate and detergent-insoluble PrP enriched by two-cycle ultracentrifugation were detected by immunoblotting and their relative amounts were estimated according to a standard curve plotted between the amount of PrP and signal intensity on immunoblotting. The titer of infectivity was determined by the incubation periods of mice inoculated with the unfractionated homogenate on the basis of a standard curve plotted between the titer and incubation period. 3. Detergent-insoluble PrP became detectable 4 weeks postinoculation (p.i.) well before the detection of PrP(Sc). The low level of detergent-insoluble PrP continued until dramatic accumulation occurred at 14 weeks p.i., correlating well with the accumulation of PrP(Sc) and development of pathological changes. The infectious titer was undetectable at 4 weeks p.i. and its logarithmic increase occurred 10 weeks p.i. preceding the logarithmic accumulation of PrPs. 4. The lag time of detergent-insoluble PrP accumulation and the discrepancy between infectious titers and PrPs observed during the early period after inoculation suggest a slow and rate-limiting step for the detergent-insoluble PrP to become the infectious agent-associated PrP(Sc)."},"publication_date":"2000-12","publication_name":{"en":"Cellular and Molecular Neurobiology","ja":"Cellular and Molecular Neurobiology"},"volume":"Vol.20","number":"No.6","starting_page":"717","ending_page":"730","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1023/A:1007054909662"],"issn":["0272-4340"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:63, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/11073804","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-0033678443&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143191","label":"url"}],"paper_title":{"en":"Physiological expression of the gene for PrP-like protein, PrPLP/Dpl, by brain endothelial cells and its ectopic expression in neurons of PrP-deficient mice ataxic due to Purkinje cell degeneration.","ja":"Physiological expression of the gene for PrP-like protein, PrPLP/Dpl, by brain endothelial cells and its ectopic expression in neurons of PrP-deficient mice ataxic due to Purkinje cell degeneration."},"authors":{"en":[{"name":"Li Aimin"},{"name":"Sakaguchi Suehiro"},{"name":"Shigematsu Kazuto"},{"name":"Atarashi Ryuichiro"},{"name":"Roy C. Bhabesh"},{"name":"Nakaoke Ryota"},{"name":"Arima Kazuhiko"},{"name":"Okimura Nobuhiko"},{"name":"Kopacek Juraj"},{"name":"Katamine Shigeru"}],"ja":[{"name":"Li Aimin"},{"name":"坂口 末廣"},{"name":"Shigematsu Kazuto"},{"name":"Atarashi Ryuichiro"},{"name":"Roy C. Bhabesh"},{"name":"Nakaoke Ryota"},{"name":"Arima Kazuhiko"},{"name":"Okimura Nobuhiko"},{"name":"Kopacek Juraj"},{"name":"Katamine Shigeru"}]},"description":{"en":"Recently, a novel gene encoding a prion protein (PrP)-like glycoprotein, PrPLP/Dpl, was identified as being expressed ectopically by neurons of the ataxic PrP-deficient (PRNP(-/-)) mouse lines exhibiting Purkinje cell degeneration. In adult wild-type mice, PrPLP/Dpl mRNA was physiologically expressed at a high level by testis and heart, but was barely detectable in brain. However, transient expression of PrPLP/Dpl mRNA was detectable by Northern blotting in the brain of neonatal wild-type mice, showing maximal expression around 1 week after birth. In situ hybridization paired with immunohistochemistry using anti-factor VIII serum identified brain endothelial cells as expressing the transcripts. Moreover, in the neonatal wild-type mice, the PrPLP/Dpl mRNA colocalized with factor VIII immunoreactivities in spleen and was detectable on capillaries in lamina propria mucosa of gut. These findings suggested a role of PrPLP/Dpl in angiogenesis, in particular blood-brain barrier maturation in the central nervous system. Even in the ataxic Ngsk PRNP(-/-) mice, the physiological regulation of PrPLP/Dpl mRNA expression in brain endothelial cells was still preserved. This strongly supports the argument that the ectopic expression of PrPLP/Dpl in neurons, but not deregulation of its physiological expression in endothelial cells, is involved in the neuronal degeneration in ataxic PRNP(-/-) mice.","ja":"Recently, a novel gene encoding a prion protein (PrP)-like glycoprotein, PrPLP/Dpl, was identified as being expressed ectopically by neurons of the ataxic PrP-deficient (PRNP(-/-)) mouse lines exhibiting Purkinje cell degeneration. In adult wild-type mice, PrPLP/Dpl mRNA was physiologically expressed at a high level by testis and heart, but was barely detectable in brain. However, transient expression of PrPLP/Dpl mRNA was detectable by Northern blotting in the brain of neonatal wild-type mice, showing maximal expression around 1 week after birth. In situ hybridization paired with immunohistochemistry using anti-factor VIII serum identified brain endothelial cells as expressing the transcripts. Moreover, in the neonatal wild-type mice, the PrPLP/Dpl mRNA colocalized with factor VIII immunoreactivities in spleen and was detectable on capillaries in lamina propria mucosa of gut. These findings suggested a role of PrPLP/Dpl in angiogenesis, in particular blood-brain barrier maturation in the central nervous system. Even in the ataxic Ngsk PRNP(-/-) mice, the physiological regulation of PrPLP/Dpl mRNA expression in brain endothelial cells was still preserved. This strongly supports the argument that the ectopic expression of PrPLP/Dpl in neurons, but not deregulation of its physiological expression in endothelial cells, is involved in the neuronal degeneration in ataxic PRNP(-/-) mice."},"publication_date":"2000-11","publication_name":{"en":"The American Journal of Pathology","ja":"The American Journal of Pathology"},"volume":"Vol.157","number":"No.5","starting_page":"1447","ending_page":"1452","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/S0002-9440(10)64782-7"],"issn":["0002-9440"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:64, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/10930132","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-0033942010&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143195","label":"url"}],"paper_title":{"en":"Identification of a novel gene encoding a PrP-like protein expressed as chimeric transcripts fused to PrP exon 1/2 in ataxic mouse line with a disrupted PrP gene.","ja":"Identification of a novel gene encoding a PrP-like protein expressed as chimeric transcripts fused to PrP exon 1/2 in ataxic mouse line with a disrupted PrP gene."},"authors":{"en":[{"name":"Li Aimin"},{"name":"Sakaguchi Suehiro"},{"name":"Atarashi Ryuichiro"},{"name":"Roy C. Bhabesh"},{"name":"Nakaoke Ryota"},{"name":"Arima Kazuhiko"},{"name":"Okimura Nobuhiko"},{"name":"Kopacek Juraj"},{"name":"Shigematsu Kazuto"}],"ja":[{"name":"Li Aimin"},{"name":"坂口 末廣"},{"name":"Atarashi Ryuichiro"},{"name":"Roy C. Bhabesh"},{"name":"Nakaoke Ryota"},{"name":"Arima Kazuhiko"},{"name":"Okimura Nobuhiko"},{"name":"Kopacek Juraj"},{"name":"Shigematsu Kazuto"}]},"description":{"en":"1. Mouse lines lacking prion protein (PrP(C)) have a puzzling phenotypic discrepancy. Some, but not all, developed late-onset ataxia due to Purkinje cell degeneration. 2. Here, we identified aberrant mRNA species in the brain of Ngsk Prnp0/0 ataxic, but not in nonataxic Zrch Prnp0/0 mouse line. These mRNAs were chimeric between the noncoding exons 1 and 2 of the PrP gene (Prnp) and the novel sequence encoding PrP-like protein (PrPLP), a putative membrane glycoprotein with 23% identity to PrP(C) in the primary amino acid structure. The chimeric mRNAs were generated from the disrupted Prnp locus of Ngsk Prnp0/0 mice lacking a part of the Prnp intron 2 and its splice acceptor signal. 3. In the brain of wild-type and Zrch Prnp0/0 mice, PrPLP mRNA was barely detectable. In contrast, in the brain of Ngsk Prnp0/0 mice, PrP/PrPLP chimeric mRNAs were expressed in neurons, at a particularly high level in hippocampus pyramidal cells and Purkinje cells under the control of the Prnp promoter. 4. In addition to the functional loss of PrP(C), ectopic PrPLP expression from the chimeric mRNAs could also be involved in the Purkinje cell degeneration in Ngsk Prnp0/0 mice.","ja":"1. Mouse lines lacking prion protein (PrP(C)) have a puzzling phenotypic discrepancy. Some, but not all, developed late-onset ataxia due to Purkinje cell degeneration. 2. Here, we identified aberrant mRNA species in the brain of Ngsk Prnp0/0 ataxic, but not in nonataxic Zrch Prnp0/0 mouse line. These mRNAs were chimeric between the noncoding exons 1 and 2 of the PrP gene (Prnp) and the novel sequence encoding PrP-like protein (PrPLP), a putative membrane glycoprotein with 23% identity to PrP(C) in the primary amino acid structure. The chimeric mRNAs were generated from the disrupted Prnp locus of Ngsk Prnp0/0 mice lacking a part of the Prnp intron 2 and its splice acceptor signal. 3. In the brain of wild-type and Zrch Prnp0/0 mice, PrPLP mRNA was barely detectable. In contrast, in the brain of Ngsk Prnp0/0 mice, PrP/PrPLP chimeric mRNAs were expressed in neurons, at a particularly high level in hippocampus pyramidal cells and Purkinje cells under the control of the Prnp promoter. 4. In addition to the functional loss of PrP(C), ectopic PrPLP expression from the chimeric mRNAs could also be involved in the Purkinje cell degeneration in Ngsk Prnp0/0 mice."},"publication_date":"2000-10","publication_name":{"en":"Cellular and Molecular Neurobiology","ja":"Cellular and Molecular Neurobiology"},"volume":"Vol.20","number":"No.5","starting_page":"553","ending_page":"567","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1023/A:1007059827541"],"issn":["0272-4340"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:65, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/10590130","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-0033987067&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143200","label":"url"}],"paper_title":{"en":"Upregulation of the genes encoding lysosomal hydrolases, a perforin-like protein, and peroxidases in the brains of mice affected with an experimental prion disease.","ja":"Upregulation of the genes encoding lysosomal hydrolases, a perforin-like protein, and peroxidases in the brains of mice affected with an experimental prion disease."},"authors":{"en":[{"name":"Kopacek Juraj"},{"name":"Sakaguchi Suehiro"},{"name":"Shigematsu Kazuto"},{"name":"Nishida Noriyuki"},{"name":"Atarashi Ryuichiro"},{"name":"Nakaoke Ryota"},{"name":"Moriuchi Ryozo"},{"name":"Niwa Masami"},{"name":"Katamine Shigeru"}],"ja":[{"name":"Kopacek Juraj"},{"name":"坂口 末廣"},{"name":"Shigematsu Kazuto"},{"name":"Nishida Noriyuki"},{"name":"Atarashi Ryuichiro"},{"name":"Nakaoke Ryota"},{"name":"Moriuchi Ryozo"},{"name":"Niwa Masami"},{"name":"Katamine Shigeru"}]},"description":{"en":"In an attempt to identify the molecules involved in the pathogenesis of prion diseases, we performed cDNA subtraction on the brain tissues of mice affected with an experimental prion disease and the unaffected control. The genes identified as being upregulated in the prion-affected brain tissue included those encoding a series of lysosomal hydrolases (lysozyme M and both isoforms of beta-N-acetylhexosaminidase), a perforin-like protein (macrophage proliferation-specific gene-1 [MPS-1]), and an oxygen radical scavenger (peroxiredoxin). Dramatic increases in the expression level occurred at between 12 and 16 weeks after intracerebral inoculation of the prion, coinciding with the onset of spongiform degeneration. The proteinase K-resistant prion protein (PrP(Sc)) became detectable by immunoblotting well before 12 weeks, suggesting a causal relationship between this and the gene activation. Immunohistochemistry paired with in situ hybridization on sections of the affected brain tissue revealed that expression of the peroxiredoxin gene was detectable only in astrocytes and was noted throughout the affected brain tissue. On the other hand, the genes for the lysosomal hydrolases and MPS-1 were overexpressed exclusively by microglia, which colocalized with the spongiform morphological changes. A crucial role for microglia in the spongiform degeneration by their production of neurotoxic substances, and possibly via the aberrant activation of the lysosomal system, would have to be considered.","ja":"In an attempt to identify the molecules involved in the pathogenesis of prion diseases, we performed cDNA subtraction on the brain tissues of mice affected with an experimental prion disease and the unaffected control. The genes identified as being upregulated in the prion-affected brain tissue included those encoding a series of lysosomal hydrolases (lysozyme M and both isoforms of beta-N-acetylhexosaminidase), a perforin-like protein (macrophage proliferation-specific gene-1 [MPS-1]), and an oxygen radical scavenger (peroxiredoxin). Dramatic increases in the expression level occurred at between 12 and 16 weeks after intracerebral inoculation of the prion, coinciding with the onset of spongiform degeneration. The proteinase K-resistant prion protein (PrP(Sc)) became detectable by immunoblotting well before 12 weeks, suggesting a causal relationship between this and the gene activation. Immunohistochemistry paired with in situ hybridization on sections of the affected brain tissue revealed that expression of the peroxiredoxin gene was detectable only in astrocytes and was noted throughout the affected brain tissue. On the other hand, the genes for the lysosomal hydrolases and MPS-1 were overexpressed exclusively by microglia, which colocalized with the spongiform morphological changes. A crucial role for microglia in the spongiform degeneration by their production of neurotoxic substances, and possibly via the aberrant activation of the lysosomal system, would have to be considered."},"publication_date":"2000-01","publication_name":{"en":"Journal of Virology","ja":"Journal of Virology"},"volume":"Vol.74","number":"No.1","starting_page":"411","ending_page":"417","languages":["eng"],"referee":true,"identifiers":{"issn":["0022-538X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:66, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143172","label":"url"}],"paper_title":{"en":"PrP fragment 106-126 is toxic to cerebral endothelial cells expressing PrPC.","ja":"PrP fragment 106-126 is toxic to cerebral endothelial cells expressing PrPC."},"authors":{"en":[{"name":"Deli A. Maria"},{"name":"Sakaguchi Suehiro"},{"name":"Nakaoke Ryota"},{"name":"Abraham S. Csongor"},{"name":"Takahata Hideaki"},{"name":"Kopacek Juraj"},{"name":"Shigematsu Kazuto"},{"name":"Katamine Shigeru"},{"name":"Niwa Masami"}],"ja":[{"name":"Deli A. Maria"},{"name":"坂口 末廣"},{"name":"Nakaoke Ryota"},{"name":"Abraham S. Csongor"},{"name":"Takahata Hideaki"},{"name":"Kopacek Juraj"},{"name":"Shigematsu Kazuto"},{"name":"Katamine Shigeru"},{"name":"Niwa Masami"}]},"publication_date":"2000","publication_name":{"en":"NeuroReport","ja":"NeuroReport"},"volume":"Vol.11","number":"No.17","starting_page":"3931","ending_page":"3936","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1097/00001756-200011270-00064"],"issn":["0959-4965"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:67, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143203","label":"url"}],"paper_title":{"en":"A mouse prion protein (PrP) transgene rescues Purkinje cell degeneration and demyelination in mice deficient for PrP.","ja":"A mouse prion protein (PrP) transgene rescues Purkinje cell degeneration and demyelination in mice deficient for PrP."},"authors":{"en":[{"name":"Nishida Noriyuki"},{"name":"Tremblay Patrick"},{"name":"Sugimoto Tetsuo"},{"name":"Shigematsu Kazuto"},{"name":"Shirabe Susumu"},{"name":"Petromilli Chris"},{"name":"Erpel Pilkuhn Susanne"},{"name":"Nakaoke Ryota"},{"name":"Atarashi Ryuichiro"},{"name":"Houtani Takeshi"},{"name":"Torchia Marilyn"},{"name":"Sakaguchi Suehiro"},{"name":"DeArmond J. Stephen"},{"name":"Prusiner B. Stanley"},{"name":"Katamine Shigeru"}],"ja":[{"name":"Nishida Noriyuki"},{"name":"Tremblay Patrick"},{"name":"Sugimoto Tetsuo"},{"name":"Shigematsu Kazuto"},{"name":"Shirabe Susumu"},{"name":"Petromilli Chris"},{"name":"Erpel Pilkuhn Susanne"},{"name":"Nakaoke Ryota"},{"name":"Atarashi Ryuichiro"},{"name":"Houtani Takeshi"},{"name":"Torchia Marilyn"},{"name":"坂口 末廣"},{"name":"DeArmond J. Stephen"},{"name":"Prusiner B. Stanley"},{"name":"Katamine Shigeru"}]},"publication_date":"1999","publication_name":{"en":"Laboratory Investigation","ja":"Laboratory Investigation"},"volume":"Vol.79","number":"No.6","starting_page":"689","ending_page":"697","languages":["eng"],"referee":true,"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:68, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/9876879","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143766","label":"url"}],"paper_title":{"en":"Impaired motor coordination in mice lacking prion protein.","ja":"Impaired motor coordination in mice lacking prion protein."},"authors":{"en":[{"name":"Katamine Shigeru"},{"name":"Nishida Noriuki"},{"name":"Sugimoto Tetsuo"},{"name":"Noda Tetsuo"},{"name":"Sakaguchi Suehiro"},{"name":"Shigematsu Kazuto"},{"name":"Kataoka Yasufumi"},{"name":"Nakatani Akira"},{"name":"Hasegawa Sumitaka"},{"name":"Moriuchi Ryozo"},{"name":"Miyamoto Tsutomu"}],"ja":[{"name":"Katamine Shigeru"},{"name":"Nishida Noriuki"},{"name":"Sugimoto Tetsuo"},{"name":"Noda Tetsuo"},{"name":"坂口 末廣"},{"name":"Shigematsu Kazuto"},{"name":"Kataoka Yasufumi"},{"name":"Nakatani Akira"},{"name":"Hasegawa Sumitaka"},{"name":"Moriuchi Ryozo"},{"name":"Miyamoto Tsutomu"}]},"description":{"en":"1. Prion protein (PrPC) is a host-encoded glycoprotein constitutively expressed on the neuronal cell surface. Accumulation of its protease-resistant isoform is closely related to pathologic changes and prion propagation in the brain tissue of a series of prion diseases. However, the physiological role of PrPC remains to be elucidated. 2. After long-term observation, we noted impaired motor coordination and loss of cerebellar Purkinje cells in the aged mice homozygous for a disrupted PrP gene, a finding which strongly suggests that PrPC plays a role in the long-term survival of Purkinje cells. 3. We also describe the resistance of the PrP null mice to the prion, indicating the requirement of PrPC for both the development of prion diseases and the prion propagation.","ja":"1. Prion protein (PrPC) is a host-encoded glycoprotein constitutively expressed on the neuronal cell surface. Accumulation of its protease-resistant isoform is closely related to pathologic changes and prion propagation in the brain tissue of a series of prion diseases. However, the physiological role of PrPC remains to be elucidated. 2. After long-term observation, we noted impaired motor coordination and loss of cerebellar Purkinje cells in the aged mice homozygous for a disrupted PrP gene, a finding which strongly suggests that PrPC plays a role in the long-term survival of Purkinje cells. 3. We also describe the resistance of the PrP null mice to the prion, indicating the requirement of PrPC for both the development of prion diseases and the prion propagation."},"publication_date":"1998-12","publication_name":{"en":"Cellular and Molecular Neurobiology","ja":"Cellular and Molecular Neurobiology"},"volume":"Vol.18","number":"No.6","starting_page":"731","ending_page":"742","languages":["eng"],"referee":true,"identifiers":{"issn":["0272-4340"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:69, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/8606772","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143767","label":"url"}],"paper_title":{"en":"Loss of cerebellar Purkinje cells in aged mice homozygous for a disrupted PrP gene.","ja":"Loss of cerebellar Purkinje cells in aged mice homozygous for a disrupted PrP gene."},"authors":{"en":[{"name":"Sakaguchi Suehiro"},{"name":"Katamine Shigeru"},{"name":"Nishida Noriyuki"},{"name":"Moriuchi Ryozo"},{"name":"Shigematsu Kazuto"},{"name":"Sugimoto Tetsuo"},{"name":"Nakatani Akira"},{"name":"Kataoka Yasufumi"},{"name":"Houtani Takeshi"},{"name":"Shirabe Susumu"},{"name":"Okada Hitoshi"},{"name":"Hasegawa Sumitaka"},{"name":"Miyamoto Tsutomu"},{"name":"Noda Tetsuo"}],"ja":[{"name":"坂口 末廣"},{"name":"Katamine Shigeru"},{"name":"Nishida Noriyuki"},{"name":"Moriuchi Ryozo"},{"name":"Shigematsu Kazuto"},{"name":"Sugimoto Tetsuo"},{"name":"Nakatani Akira"},{"name":"Kataoka Yasufumi"},{"name":"Houtani Takeshi"},{"name":"Shirabe Susumu"},{"name":"Okada Hitoshi"},{"name":"Hasegawa Sumitaka"},{"name":"Miyamoto Tsutomu"},{"name":"Noda Tetsuo"}]},"description":{"en":"Prion protein (PrP) is a glycoprotein constitutively expressed on the neuronal cell surface. A protease-resistant isoform of prion protein is implicated in the pathogenesis of a series of transmissible spongiform encephalopathies. We have developed a line of mice homozygous for a disrupted PrP gene in which the whole PrP-coding sequence is replaced by a drug-resistant gene. In keeping with previous results, we find that homozygous loss of the PrP gene has no deleterious effect on the development of these mice and renders them resistant to prion. The PrP-null mice grew normally after birth, but at about 70 weeks of age all began to show progressive symptoms of ataxia. Impaired motor coordination in these ataxic mice was evident in a rotorod test. Pathological examination revealed an extensive loss of Purkinje cells in the vast majority of cerebellar folia, suggesting that PrP plays a role in the long-term survival of Purkinje neurons.","ja":"Prion protein (PrP) is a glycoprotein constitutively expressed on the neuronal cell surface. A protease-resistant isoform of prion protein is implicated in the pathogenesis of a series of transmissible spongiform encephalopathies. We have developed a line of mice homozygous for a disrupted PrP gene in which the whole PrP-coding sequence is replaced by a drug-resistant gene. In keeping with previous results, we find that homozygous loss of the PrP gene has no deleterious effect on the development of these mice and renders them resistant to prion. The PrP-null mice grew normally after birth, but at about 70 weeks of age all began to show progressive symptoms of ataxia. Impaired motor coordination in these ataxic mice was evident in a rotorod test. Pathological examination revealed an extensive loss of Purkinje cells in the vast majority of cerebellar folia, suggesting that PrP plays a role in the long-term survival of Purkinje neurons."},"publication_date":"1996-04-11","publication_name":{"en":"Nature","ja":"Nature"},"volume":"Vol.380","number":"No.6574","starting_page":"528","ending_page":"531","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/380528a0"],"issn":["0028-0836"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:70, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143768","label":"url"}],"paper_title":{"en":"Accumulation of proteinase K-resistant prion protein (PrP) is restricted by the expression level of normal PrP in mice inoculated with a mouse-adapted strain of the Creutzfeldt-Jakob disease agent.","ja":"Accumulation of proteinase K-resistant prion protein (PrP) is restricted by the expression level of normal PrP in mice inoculated with a mouse-adapted strain of the Creutzfeldt-Jakob disease agent."},"authors":{"en":[{"name":"Sakaguchi Suehiro"},{"name":"Katamine Shigeru"},{"name":"Shigematsu Kazuto"},{"name":"Nakatani Akira"},{"name":"Moriuchi Ryozo"},{"name":"Nishida Noriyuki"},{"name":"Kurokawa Kenji"},{"name":"Nakaoke Ryota"},{"name":"Sato Hiroshi"},{"name":"Jishage Kouichi"},{"name":"Kuno Junko"},{"name":"Noda Tetsuo"},{"name":"Miyamoto Tsutomu"}],"ja":[{"name":"坂口 末廣"},{"name":"Katamine Shigeru"},{"name":"Shigematsu Kazuto"},{"name":"Nakatani Akira"},{"name":"Moriuchi Ryozo"},{"name":"Nishida Noriyuki"},{"name":"Kurokawa Kenji"},{"name":"Nakaoke Ryota"},{"name":"Sato Hiroshi"},{"name":"Jishage Kouichi"},{"name":"Kuno Junko"},{"name":"Noda Tetsuo"},{"name":"Miyamoto Tsutomu"}]},"publication_date":"1995","publication_name":{"en":"Journal of Virology","ja":"Journal of Virology"},"volume":"Vol.69","number":"No.12","starting_page":"7586","ending_page":"7592","languages":["eng"],"referee":true,"identifiers":{"issn":["0022-538X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:71, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143771","label":"url"}],"paper_title":{"en":"The infectivity is dissociated from PrP accumulation in salivary gland of Creutzfeldt-Jakob disease agent-inoculated mice.","ja":"The infectivity is dissociated from PrP accumulation in salivary gland of Creutzfeldt-Jakob disease agent-inoculated mice."},"authors":{"en":[{"name":"Miyamoto Tsutomu"},{"name":"Sakaguchi Suehiro"},{"name":"Katamine Shigeru"},{"name":"Moriuchi Ryozo"}],"ja":[{"name":"Miyamoto Tsutomu"},{"name":"坂口 末廣"},{"name":"Katamine Shigeru"},{"name":"Moriuchi Ryozo"}]},"publication_date":"1994","publication_name":{"en":"Annals of the New York Academy of Sciences","ja":"Annals of the New York Academy of Sciences"},"volume":"Vol.724","starting_page":"310","ending_page":"313","languages":["eng"],"referee":true,"identifiers":{"issn":["0077-8923"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:72, {"insert":{"user_id":"5000035549","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/8409936","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=143772","label":"url"}],"paper_title":{"en":"Kinetics of infectivity are dissociated from PrP accumulation in salivary glands of Creutzfeldt-Jakob disease agent-inoculated mice.","ja":"Kinetics of infectivity are dissociated from PrP accumulation in salivary glands of Creutzfeldt-Jakob disease agent-inoculated mice."},"authors":{"en":[{"name":"Sakaguchi Suehiro"},{"name":"Katamine Shigeru"},{"name":"Yamanouchi Kouichi"},{"name":"Kishikawa Masao"},{"name":"Moriuchi Ryozo"},{"name":"Yasukawa Norio"},{"name":"Doi Takashi"},{"name":"Miyamoto Tsutomu"}],"ja":[{"name":"坂口 末廣"},{"name":"Katamine Shigeru"},{"name":"Yamanouchi Kouichi"},{"name":"Kishikawa Masao"},{"name":"Moriuchi Ryozo"},{"name":"Yasukawa Norio"},{"name":"Doi Takashi"},{"name":"Miyamoto Tsutomu"}]},"description":{"en":"The protease-resistant isoform of prion protein (PrP) has been implicated in the pathogenesis and transmission of Creutzfeldt-Jakob disease (CJD), scrapie and other related diseases, but the relationship between the infectious agent and PrP awaits elucidation. In the present study, we have examined levels of infectivity together with accumulation of the protease-resistant form of PrP (PrPCJD) in various tissues of CJD agent-inoculated mice. Accumulation of PrPCJD occurred only in tissues, including brain, salivary gland and spleen, in which infectivity was readily detectable throughout the course of the experiment. The brain showed the highest levels of both infectivity and PrPCJD accumulation, with well correlated kinetics. On the other hand, the high titres of infectivity detected in salivary gland and spleen early after inoculation of the agent were obviously distinguishable from PrPCJD. Furthermore, in the salivary gland, the kinetics of infectivity and the accumulation of PrPCJD reversed; infectivity declined as PrPCJD accumulated in the tissue. Our findings indicate that PrPCJD accumulation is associated with replication of the agent; however, PrPCJD is unlikely to be the agent itself.","ja":"The protease-resistant isoform of prion protein (PrP) has been implicated in the pathogenesis and transmission of Creutzfeldt-Jakob disease (CJD), scrapie and other related diseases, but the relationship between the infectious agent and PrP awaits elucidation. In the present study, we have examined levels of infectivity together with accumulation of the protease-resistant form of PrP (PrPCJD) in various tissues of CJD agent-inoculated mice. Accumulation of PrPCJD occurred only in tissues, including brain, salivary gland and spleen, in which infectivity was readily detectable throughout the course of the experiment. The brain showed the highest levels of both infectivity and PrPCJD accumulation, with well correlated kinetics. On the other hand, the high titres of infectivity detected in salivary gland and spleen early after inoculation of the agent were obviously distinguishable from PrPCJD. Furthermore, in the salivary gland, the kinetics of infectivity and the accumulation of PrPCJD reversed; infectivity declined as PrPCJD accumulated in the tissue. Our findings indicate that PrPCJD accumulation is associated with replication of the agent; however, PrPCJD is unlikely to be the agent itself."},"publication_date":"1993-10","publication_name":{"en":"The Journal of General Virology","ja":"The Journal of General Virology"},"volume":"Vol.74","number":"No.Pt10","starting_page":"2117","ending_page":"2123","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1099/0022-1317-74-10-2117"],"issn":["0022-1317"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
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