The Association Between ß-Glucocerebrosidase Mutations and Parkinsonism

摘要: Mutations in the s-glucocerebrosidase gene (GBA), which encodes lysosomal enzyme s-glucocerebrosidase, have traditionally been implicated Gaucher disease, an autosomal recessive storage disorder. Yet past two decades yielded explosion of epidemiological and basic-science evidence linking mutations GBA with development Parkinson disease (PD) as well. Although specific contribution mutant to pathogenesis parkinsonism remains unknown, suggests that both loss function toxic gain by abnormal may be important, implicates a close relationship between α-synuclein. Furthermore, multiple lines suggest although GBA-associated PD closely mimics idiopathic (IPD), it present at younger age, is more frequently complicated cognitive dysfunction. Understanding clinical association PD, α-synuclein, enhance understanding IPD, improve prognostication treatment carriers parkinsonism, furthermore inform therapies for IPD not due mutations.