Exploring the link between glucocerebrosidase mutations and parkinsonism.

ABSTRACT: Clinical, genetic and pathological studies demonstrate that mutations in glucocerebrosidase (GBA), which encodes the lysosomal enzyme deficient in Gaucher disease (GD), are risk factors for Parkinson disease (PD) and related disorders. Some patients with GD and Gaucher carriers develop parkinsonism. Furthermore, subjects with PD have an increased frequency of GBA mutations. GBA-mutation carriers exhibit diverse parkinsonian phenotypes and have glucocerebrosidase-positive Lewy bodies. Although the mechanism for this association is unknown, we present several theories, including protein aggregation, prion transmission, lipid accumulation and impaired autophagy, mitophagy or trafficking. Each model has inherent limitations, and a second-hit mutation might be essential. Elucidation of the basi

SUBMITTER: Westbroek W 

PROVIDER: S-EPMC3351003 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature