The Eole of LRRK2 G2019S Mutation in Neuroinflammatory Processes and Its Relevance for Parkinson's Disease

Abstract

Pa ki so s disease (PD) has been linked to a variety of environmental and immunological challenges involving both oxidative and inflammatory processes, however, genetics also clearly plays a role in vulnerability to such insults. Indeed, the Gly-2019-Ser (G2019S) leucine rich repeat kinase (LRRK2) mutation is the most common mutation enriched compared to controls in both familial and sporadic Pa ki so s patie ts. Our current study focuses on the interplay between the G2019S genetic mutation and exposure to the bacterial endotoxin, lipopolysaccharide (LPS). In the current study mice were centrally infused with either vehicle or one of two doses of LPS (2 or 10ug) in order to determine whether an inflammatory based insult would produce augmented pathology in G2019S mutant mice. Infusion of LPS into the substantia nigra pars compacta (SNc; the region containing dopamine neurons which degenerate in PD) produced a (non-statistically significant) trend towards a dose-dependent reduction in