Figure 1

Abnormal activity of or mutations LRRK2 might push microglia cells toward a pro-inflammatory phenotype. Abnormal LRRK2 activity might modulate microglia cell activation and phagocytosis through hyperphosphorylation and hyperpolymerization of cytoskeleton components such as actin and β-tubulin. Moreover, LRRK2 might regulate the delivery of membrane receptors (CD11b and MHC- II) and inflammatory cytokines through regulation of transcription factors (such as NF-κB), and interaction and phoshorylation of vesicle-associated proteins such as Rab GTPase and NSF, thus driving microglia toward a reactive phenotype with enhanced cell activity and inflammation in response to inflammatory stimuli including LPS, environmental insults, and neuronal susceptibility.