| 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)
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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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