Analysis of LRRK2-function in microglial alpha-synuclein clearance
Project/Area Number |
25860720
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Neurology
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Research Institution | Kitasato University |
Principal Investigator |
|
Project Period (FY) |
2013-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | ミクログリア / パーキンソン病 / alpha-synuclein / LRRK2 / αシヌクレイン |
Outline of Final Research Achievements |
In this study, we investigated alpha-synuclein clearance by microglia isolated from LRRK2-knockout (KO) mice and found that alpha-synuclein was taken up in larger amounts and cleared from the supernatant more effectively than from microglia isolated from wild-type (WT) mice. This higher clearance ability of LRRK2-KO microglia was thought to be ascribable to an up-regulation of early endocytotic pathway. We also analyzed TLR4-mediated TNF-alpha production by LRRK2-KO microglia upon stimulation with alpha-synuclein and found that this was decreased in comparison with WT microglia. These results indicate that LRRK2 negatively regulates the clearance of alpha-synuclein through down-regulation of the endocytosis pathway, and positively regulates the production of alpha-synuclein induced TNF-alpha production. Our findings revealed a new functional role of LRRK2 in microglia and offer a new insight into the mechanism of Parkinson's disease pathogenesis.
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Report
(3 results)
Research Products
(8 results)