The Parkinson's Disease-Associated H50Q Mutation Accelerates α-Synuclein Aggregation in Vitro

alpha-Synuclein (alpha-Syn) aggregation is directly linked with Parkinson's disease (PD) pathogenesis. Here, we analyzed the aggregation of newly discovered a-Syn missense mutant H50Q in vitro and found that this mutation significantly accelerates the aggregation and amyloid formation of alpha-Syn. This mutation, however, did not alter the overall secondary structure as suggested by two-dimensional nuclear magnetic resonance and circular dichroism spectroscopy. The initial oligomerization study by cross-linking and chromatographic techniques suggested that this mutant oligomerizes to an extent similar to that of the wild-type alpha-Syn protein. Understanding the aggregation mechanism of this H50Q mutant may help to establish the aggregation and phenotypic relationship of this novel mutant in PD.