| Project/Area Number |
25870441
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurology
Neurochemistry/Neuropharmacology
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| Research Institution | Tottori University |
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Principal Investigator |
ITO Satoru 鳥取大学, 医学部附属病院, 助教 (20448195)
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| Research Collaborator |
NAKASO Kazuhiro
NAKASHIMA Kenji
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | パーキンソン病 / 小胞体 / TRPC1チャネル / カルシウムチャネル / モデル細胞 / PC12細胞 / ミトコンドリア毒性 / SOCE機構 / αシヌクレイン / TRPC1 / SOCE / ミトコンドリア / 過剰発現 / 培養細胞 / 細胞死 |
|---|
| Outline of Final Research Achievements |
The endogenous store-operated calcium entry (SOCE) mechanism via TRPC1 channel is important to the maintenance of endoplasmic reticulum function. In recent years, a decreased expression level of TRPC1 was shown in the autopsied brain of Parkinson's disease (PD) patients. In addition, α-synuclein (AS) is also known to have cytotoxicity to the dopaminergic cells in PD.
We investigated the association between SOCE mechanism and AS pathology. We constructed PC12 cell line which overexpressed human AS. The expression level of TRPC1 was decreased by stimulation of mitochondrial stressors. Overexpression of human α-synuclein did not affect the TRPC1 suppression seen in mitochondrial stressor exposures. Meanwhile, TRPC1 inhibitor increased α-synuclein cytotoxicity.
According to these results, it is considered that mitochondrial stressors causes dysfunction of SOCE by inhibition of TRPC1 expression, and TRPC1 inhibition may lead to enhance the α-synuclein cytotoxicity.
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