Lrrk promotes tau neurotoxicity through dysregulation of actin and mitochondrial dynamics.

ABSTRACT: Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson disease. Genetics and neuropathology link Parkinson disease with the microtubule-binding protein tau, but the mechanism of action of LRRK2 mutations and the molecular connection between tau and Parkinson disease are unclear. Here, we investigate the interaction of LRRK and tau in Drosophila and mouse models of tauopathy. We find that either increasing or decreasing the level of fly Lrrk enhances tau neurotoxicity, which is further exacerbated by expressing Lrrk with dominantly acting Parkinson disease-associated mutations. At the cellular level, altering Lrrk expression promotes tau neurotoxicity via excess stabilization of filamentous actin (F-actin) and subsequent mislocalization of the crit

SUBMITTER: Bardai FH 

PROVIDER: S-EPMC6319772 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature