Lysosomal Pathogenesis of Parkinson's Disease: Insights From LRRK2 and GBA1 Rodent Models.

ABSTRACT: The discovery of mutations in LRRK2 and GBA1 that are linked to Parkinson's disease provided further evidence that autophagy and lysosome pathways are likely implicated in the pathogenic process. Their protein products are important regulators of lysosome function. LRRK2 has kinase-dependent effects on lysosome activity, autophagic efficacy and lysosomal Ca²⁺ signaling. Glucocerebrosidase (encoded by GBA1) is a hydrolytic enzyme contained in the lysosomes and contributes to the degradation of alpha-synuclein. PD-related mutations in LRRK2 and GBA1 slow the degradation of alpha-synuclein, thus directly implicating the dysfunction of the process in the neuropathology of Parkinson's disease. The development of genetic rodent models of LRRK2 and GBA1 provided hopes of obtaining reli

SUBMITTER: Volta M 

PROVIDER: S-EPMC10119359 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature