Kinetic model of the aggregation of alpha-synuclein provides insights into prion-like spreading.

ABSTRACT: The protein alpha-synuclein (αS) self-assembles into small oligomeric species and subsequently into amyloid fibrils that accumulate and proliferate during the development of Parkinson's disease. However, the quantitative characterization of the aggregation and spreading of αS remains challenging to achieve. Previously, we identified a conformational conversion step leading from the initially formed oligomers to more compact oligomers preceding fibril formation. Here, by a combination of single-molecule fluorescence measurements and kinetic analysis, we find that the reaction in solution involves two unimolecular structural conversion steps, from the disordered to more compact oligomers and then to fibrils, which can elongate by further monomer addition. We have obtained individual rate con

SUBMITTER: Iljina M 

PROVIDER: S-EPMC4780632 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature