• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2014 Fiscal Year Final Research Report

Analysis of LRRK2-function in microglial alpha-synuclein clearance

Research Project

  • PDF
Project/Area Number 25860720
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurology
Research InstitutionKitasato University

Principal Investigator

MAEKAWA Tatsunori  北里大学, 医療衛生学部, 助教 (30647673)

Project Period (FY) 2013-04-01 – 2015-03-31
Keywordsミクログリア / パーキンソン病 / alpha-synuclein / LRRK2
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.

Free Research Field

神経変性疾患

URL: 

Published: 2016-06-03  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi