Aggregation of alpha-synuclein and mechanisms of cell death

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