2014 Fiscal Year Final Research Report
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 |
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| Research Field |
Neurology
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | ミクログリア / パーキンソン病 / alpha-synuclein / LRRK2 |
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| 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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| Free Research Field |
神経変性疾患
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