Mechanisms of Neuronal Death in Synucleinopathy

alpha-synuclein is a key molecule in the pathogenesis of synucleinopathy including Parkinson's disease and multiple system atrophy. In this mini-review, we mainly focus on recent data obtained from cellular models of synucleinopathy and discuss the possible mechanisms of neurodegeneration. Recent progress suggests that the aggregate formation of alpha-synuclein is cytoprotective and that its precursor oligomer (protofibril) may be cytotoxic. The catechol-derived quinones are the candidate molecules that facilitate the oligomer formation of alpha-synuclein. Furthermore, the cellular membranes are shown to be the primary targets injured by mutant alpha-synucleins, and the mitochondrial dysfunction seems to be an initial step in the neuronal death.