Understanding the role of parkin in Parkinson's disease

Abstract

The recent linkage of genetic mutations in the parkin gene to familial Parkinson's disease (PD) and the seminal discovery that parkin functions as an ubiquitin ligase associated with the ubiquitin-proteasome system have been instrumental in shaping our understanding of PD pathogenesis. Currently, mutations in parkin are recognised as the most common cause of familial PD. Emerging evidence also suggests a role for parkin in dopaminergic neuronal dysfunction as well as Lewy body biogenesis in the more common sporadic PD. The relevance of parkin in PD is thus compelling. In this review, we highlight several significant discoveries made recently regarding parkin function that support its role in both familial and idiopathic PD. We will also discuss the phenotypes of a number of mouse models of parkin function that have been generated based on the targeted ablation of the parkin gene.