| Project/Area Number |
26870114
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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 |
Biological pharmacy
Nerve anatomy/Neuropathology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Kuwahara Tomoki 東京大学, 医学(系)研究科(研究院), 助教 (10533903)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | パーキンソン病 / LRRK2 / 細胞内輸送 / エンドソーム / リソソーム / 脳神経疾患 |
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| Outline of Final Research Achievements |
LRRK2 and RAB7L1, two genes related to Parkinson's disease, are implicated in the regulation of intracellular transport mediated by subcellular organelles such as endosomes and lysosomes. Here we showed the existence of RAB7L1-LRRK2 genetic pathway in mice and nematodes, and demonstrated that lysosome-related adaptor protein complex AP-3 acts as a candidate downstream effector of RAB7L1-LRRK2 pathway. We also found the evidence that lysosome has a key role in the intraneuronal accumulation of alpha-synuclein, a major hallmark pathology in Parkinson's disease brains. Collectively, these results suggest that lysosomal impairment may underlie an important mechanism in the pathogenesis of Parkinson's disease.
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