LRRK2 modulates microglial activity through regulation of chemokine (C-X3-C) receptor 1 -mediated signalling pathways.

ABSTRACT: Multiple missense mutations in Leucine-rich repeat kinase 2 (LRRK2) have been linked to Parkinson's disease (PD), the most common degenerative movement disorder. LRRK2 is expressed by both neurons and microglia, the residential immune cells in the brain. Increasing evidence supports a role of LRRK2 in modulating microglial activity, of which Lrrk2-null rodent microglia display less inflammatory response to endotoxin lipopolysaccharide (LPS). The underlying molecular mechanism, however, remains elusive. Chemokine (C-X3-C) receptor 1 (CX3CR1), predominantly expressed by microglia, suppresses microglial inflammation while promotes migration. Using whole-genome microarray screening, we found that Cx3cr1 mRNA levels were substantially higher in microglia derived from Lrrk2 knockout (Lrrk2^-

SUBMITTER: Ma B 

PROVIDER: S-EPMC5179946 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature