Investigation of pathophysiological mechanisms of synucleinopathy using cultured cellular model
| Project/Area Number |
21790831
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | Tohoku University |
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Principal Investigator |
KOBAYASHI Michiko Tohoku University, 大学院・医学系研究科, 非常勤講師 (40422109)
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | シヌクレイノパチー / シヌクレイン / 多系統萎縮症 / 異常タンパク凝集 / 細胞モデル / TPPP/p25 / GCI / オリゴデンドログリア / Sirtuin / αシヌクレイン / レビー小体 / TPPP / p25 / アグレソーム / 細胞死 / アポトーシス / SIRT2 |
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| Research Abstract |
To clarify the molecular mechanisms of GCI formation and subsequent oligodendroglial degeneration, we ectopically expressed α-SYN and TPPP in HEK293T and oligodendroglial KG1C cell lines. Here we showed that TPPP specifically accelerated α-SYN oligomer formation and co-immunoprecipitation analysis revealed the specific interaction of TPPP and α-SYN. Moreover, phosphorylation of α-SYN at Ser-129 facilitated the TPPP-mediated α-SYN oligomerization. TPPP facilitated α-SYN-positive cytoplasmic perinuclear inclusions mimicking GCI in both cell lines ; however, apoptotic cell death was only observed in KG1C cells. This apoptotic cell death was partly rescued by sirtuin 2 inhibition.
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Report
(3 results)
Research Products
(16 results)
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[Journal Article] In vivo visualization of alpha-synuclein deposition by carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl ]-6-[2-(fluoro)ethoxy benzoxazole positron emission tomography in multiple system atrophy.2010
Author(s)
Kikuchi A, Takeda A, Okamura N, Tashiro M, Hasegawa T, Furumoto S, Kobayashi M, Sugeno N, Baba T, Miki Y, Mori F, Wakabayashi K, Funaki Y, Iwata R, Takahashi S, Fukuda H, Arai H, Kudo Y, Yanai K, Itoyama Y.
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Journal Title
Brain 133
Pages: 1772-1778
Related Report
Peer Reviewed
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