2016 Fiscal Year Annual Research Report
神経変性疾患におけるエクソソームを介した生体内プロテオスターシス維持機構の解明
| Project/Area Number |
16H05325
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| Research Institution | Osaka University |
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Principal Investigator |
永井 義隆 大阪大学, 医学(系)研究科(研究院), 寄附講座教授 (60335354)
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| Co-Investigator(Kenkyū-buntansha) |
武内 敏秀 大阪大学, 医学系研究科, 寄附講座講師 (70600120)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 脳神経疾患 / 認知症 / ストレス / タンパク質 / 神経科学 |
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| Outline of Annual Research Achievements |
アルツハイマー病、パーキンソン病、筋萎縮性側索硬化症、ポリグルタミン病などの神経変性疾患では、様々な蛋白質のミスフォールディング・凝集が神経変性を引き起こすと考えられている。申請者らは、蛋白質ミスフォールディング・凝集を防ぐ分子シャペロンが、エクソソームを介した細胞間伝播により生体内プロテオスターシスを維持する機構が存在する可能性を考えて研究を行い、以下の成果を得た。
１）神経変性疾患モデルショウジョウバエにおいて、分子シャペロンの細胞間による神経変性病態への影響を明らかにした。
２）神経変性疾患モデルマウスにおける末梢血中エクソソーム内分子シャペロンの変動を評価した。また、プロテオーム解析により、疾患モデルマウスにおいて変動を認める候補分子を見出した。
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
平成28年度の研究において、神経変性疾患モデルでの分子シャペロンの検出感度が低かったため研究計画を繰り越したが、平成29年度にタグを付加した分子シャペロンを用いて、研究を行うことができたため。
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| Strategy for Future Research Activity |
神経変性疾患モデルマウスを用いて、血液中エクソソーム内分子シャペロンの変動を評価する。
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[Journal Article] Overexpression of ter94, Drosophila VCP, improved motor neuron degeneration induced by knockdown of TBPH, Drosophila TDP-43.2018
Author(s)
Kushimura Y., Tokuda T., Azuma Y., Yamamoto I., Mizuta I., Mizuno T., Nakagawa M., Ueyama M., Nagai Y., Yoshida H., Yamaguchi M.
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Journal Title
Am. J. Neurodegener. Dis.
Volume: 7
Pages: 11～31
Peer Reviewed
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[Presentation] Regulatory role of RNA chaperone for noncoding repeat RNA aggregation and repeat-associated translation in SCA31.2017
Author(s)
Nagai Y., Ishiguro T., Sato N., Ueyama M., Fujikake N., Yokota T., Wada K., Mizusawa H., Ishikawa K.
Organizer
The 43rd Naito Conference on Noncoding RNA：Biology, Chemistry, & Diseases
Int'l Joint Research
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[Presentation] Transgenic monkey model of the polyglutamine diseases recapitulating progressive neurological symptoms and polyglutamine protein inclusions.2017
Author(s)
Nagai Y., Tomioka I., Ishibashi H., Minakawa E.N, Motohashi H.H., Takayama O., Saito Y., Popiel H.A., Puentes S., Owari K., Nakatani T., Nogami N., Yamamoto K., Noguchi S., Nagano S., Nishino I., Ichinohe N., Wada K., Kohsaka S., Seki K.
Organizer
The 23rd World Congress of Neurology (WCN 2017)
Int'l Joint Research
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[Presentation] Balance between RNA binding proetin TDP-43 and an RNA UGGAA repeat underlies pathogenesis of spinocerebellar ataxia type 31 (SCA31) and motor neuron disease fly models.2017
Author(s)
13.Ishiguro T., Sato N., Ueyama M., Fujikake N., Sellier C., Tokuda E., Zamiri B., Gall-Duncan T., Mirceta M., Furukawa Y., Yokota T., Wada K., Taylor J.P., Pearson C.E., Charlet-Berguerand N., Mizusawa H., Nagai Y., Ishikawa K.
Organizer
The 23rd World Congress of Neurology (WCN 2017)
Int'l Joint Research
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[Presentation] Parkinson’s disease-linked DNAJC13 mutation aggravates α-synuclein-induced neurotoxicity through perturbation of endosomal trafficking.2017
Author(s)
Hasegawa T., Yoshida S., Suzuki M., Sugeno N., Kobayashi J., Ueyama M., Ezura M., Kikuchi A., Baba T., Takeda A., Mochizuki H., Nagai Y., Aoki M.
Organizer
The 23rd World Congress of Neurology (WCN 2017)
Int'l Joint Research
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[Presentation] The search for genes that modulate FUS-mediated phenotypes by Drosophila amyotrophic lateral sclerosis model.2017
Author(s)
Azuma Y., Tokuda T., Kushimura Y., Yamamoto I., Yoshida H., Mizuta I., Ueyama M., Nagai Y., Nakagawa M., Mizuno T., Yamaguchi M.
Organizer
The 23rd World Congress of Neurology (WCN 2017)
Int'l Joint Research
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[Presentation] Loss of function mutant of ter94, Drosophila VCP, partially enhanced motor neuron degeneration induced by knockdown of TBPH, Drosophila TDP-43.2017
Author(s)
Kushimura Y., Tokuda T., Azuma Y., Yamamoto I., Yoshida H., Mizuta I., Ueyama M., Nagai Y., Nakagawa M., Mizuno T., Yamaguchi M.
Organizer
The 23rd World Congress of Neurology (WCN 2017)
Int'l Joint Research
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[Presentation] The search for genes that modulate FUS-mediated phenotypes by Drosophila amyotrophic lateral sclerosis model.2017
Author(s)
Azuma Y., Tokuda T., Kushimura Y., Yamamoto I., Ueoka I., Mizuta I., Mizuno T., Nakagawa M., Ueyama M., Nagai Y., Yoshida H., Yamaguchi M.
Organizer
CSHL 2017 Neurobiology of Drosophila
Int'l Joint Research
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[Presentation] Loss of function mutant of ter94, Drosophila VCP, partially enhanced motor neuron degeneration induced by knockdown of TBPH, Drosophila TDP-43.2017
Author(s)
Kushimura Y., Tokuda T., Azuma Y., Yamamoto I., Ueoka I., Mizuta I., Mizuno T., Nakagawa M., Ueyama M., Nagai Y., Yoshida H., Yamaguchi M.
Organizer
CSHL 2017 Neurobiology of Drosophila
Int'l Joint Research
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[Presentation] Regulatory role of RNA chaperone TDP-43 for RNA misfolding and repeat-associated translation in SCA31.2017
Author(s)
Ishikawa K., Ishiguro T., Sato N., Ueyama M., Fujikake N., Sellier C., Tokuda E., Zamiri B., Gall-Duncan T., Mirceta M., Furukawa Y., Yokota T., Wada K., Taylor J.P., Pearson C.E., Charlet-Berguerand N., Mizusawa H., Nagai Y.
Organizer
67th Annual Meeting of American Society of Human Genetics
Int'l Joint Research
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[Presentation] Toxicity of dipeptide repeat proteins in C9 ALS/FTD model fly.2016
Author(s)
Ueyama M., Ishiguro T., Gendron T.F., Fujikake N., Konno T., Koyama A., Onodera O., Ishikawa K., Wada K., Petrucelli L., Nagai Y.
Organizer
4th RNA Metabolism in Neurological Disease Conference
Int'l Joint Research
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