Screening of molecules involved in the disease-associated conformational change of alpha-synuclein.
| Project/Area Number |
26640033
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
TAKAMATSU Yoshiki 公益財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野, 主任研究員 (50250204)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | αシヌクレイン / パーキンソン病 / テトラマー / TRAP1 / ミトコンドリア / トランスジェニックフライ / シヌクレイン / Trap1 / 四量体 / 立体構造認識抗体 / 重合開始メカニズム / 赤血球 / 架橋剤 / ショウジョウバエ |
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| Outline of Final Research Achievements |
Although dysregulation of the conformation of α synuclein (αS) is supposed to underlie the pathogenesis of α synucleinopathies, the mechanism is elusive. Therefore, the objective of the present study was to identify the molecule which might be involved in the formation of pathogenic αS oligomer. Based on the idea that differential expression profiles of transgenic animals bearing the wild type or PD-causing mutation A53T of αS, which is known to decrease a formation of physiological tetramer, may provide a clue regarding the mechanism of toxic oligomer formation, we performed both transcriptome and proteome analyses using transgenic flies. Notably, we found that TRAP1, a mitochondrial chaperone, was significantly reduced in the A53T fly as compared to the fly expressing wild type αS. Further analyses were performed by quantitative PCR and western blot. Taken together, these results suggest that TRAP1 might be involved in the mitochondrial dysfunction in the A53T type of PD.
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Disease-Modifying Effect of Adiponectin in Model of α-Synucleinopathie2014
Author(s)
Sekiyama K, Waragai M, Akatsu H, Sugama S, Takenouchi T, Takamatsu Y, Fujita M, Sekigawa A, Rockenstein E, Inoue S, La Spada A, Masliah E, Hashimoto M
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Journal Title
Ann Clin Transl Neurol
Volume: 1
Issue: 7
Pages: 479-489
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] P3-325 Disease Modifying Effect of Adiponectin in a Model of α-Synucleinopathies in Vitro and in Vivo.2015
Author(s)
Masaaki Waragai, Kazunari Sekiyama, Yoshiki Takamatsu, Masayo Fujita, Akio Sekigawa, Naomichi Iwai, Edward Rockenstein, Satoshi Inoue, Albert R. La Spada, Elizer Masliah, Makoto Hashimoto
Organizer
Alzheimer's Association International Conference (AAIC2015)
Place of Presentation
Washington, DC, USA
Year and Date
2015-07-18
Related Report
Int'l Joint Research
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[Book] 脳内環境辞典2017
Author(s)
高松芳樹、小池和佳子、藁谷正明、杉野弘、橋本款
Total Pages
2
Publisher
メディカルドゥ
Related Report
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