Effects of the mutations Ala30 to Pro and Ala53 to Thr on the physical and morphological properties of alpha-synuclein protein implicated in Parkinson's disease.

Alpha-synuclein (alpha-syn) protein has been found in association with the pathological lesions of a number of neurodegenerative diseases. Recently, mutations in the alpha-syn gene have been reported in families susceptible to an inherited form of Parkinson's disease. We report here that human wild-type alpha-syn, PD-linked mutant alpha-syn(Ala30Pro) and mutant alpha-syn(Ala53Thr) proteins can self-aggregate and form amyloid-like filaments. The mutant alpha-syn forms more beta-sheet and mature filaments than the wild-type protein. These findings suggest that accumulation of alpha-syn as insoluble deposits of amyloid may play a major role in the pathogenesis of these neurodegenerative diseases.