The Function of α-Synuclein

Human genetics has indicated a causal role for the protein α-synuclein in the pathogenesis of familial Parkinson’s disease (PD), and the aggregation of synuclein in essentially all patients with PD suggests a central role for this protein in the sporadic disorder. Indeed, the accumulation of misfolded α-synuclein now defines multiple forms of neural degeneration. Like many of the proteins that accumulate in other neurodegenerative disorders, however, the normal function of synuclein remains poorly understood. In this article, we review the role of synuclein at the nerve terminal and in membrane remodeling. We also consider the prion-like propagation of misfolded synuclein as a mechanism for the spread of degeneration through the neuraxis. Human genetics has indicated a causal role for the protein α-synuclein in the pathogenesis of familial Parkinson’s disease. In this Review, Bendor, Logan, and Edwards discuss the normal function of synuclein, which is not well understood, highlighting controversies surrounding its roles in nervous system function.