| Project/Area Number |
21790848
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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 | Kitasato University |
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Principal Investigator |
OHTA Etsuro Kitasato University, 医療衛生学部, 助教 (60508042)
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | パーキンソン病 / LRRK2 / 細胞内分解 / 蛋白質安定性 / アポトーシス抑制能 / V5-LRRK2安定発現細胞株 / 細胞死 |
|---|
| Research Abstract |
Mutant LRRK2 is the causal molecule for autosomal dominant familial Parkinson's disease. In the present study, we demonstrated that the protective effect of I2020T LRRK2 against hydrogen peroxide-induced apoptosis was impaired in comparison with the wild-type (WT) molecule. Also, Pulse-chase experiments proved that the I2020T LRRK2 molecule has a higher degradation rate than WT or G2019S LRRK2. Upon addition of proteasome and lysosome inhibitors, the protein level of I2020T mutant LRRK2 reached that of WT LRRK2, and simultaneously the mutant LRRK2 exhibited an elevated protective effect against apoptosis. We further confirmed that a decrease in the intracellular protein level of WT LRRK2 by knocking down resulted in a reduction of protectivity against apoptosis.
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