Direct observation of heterogeneous amyloid fibril growth kinetics via two-color super-resolution microscopy.

ABSTRACT: The self-assembly of normally soluble proteins into fibrillar amyloid structures is associated with a range of neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases. In the present study, we show that specific events in the kinetics of the complex, multistep aggregation process of one such protein, α-synuclein, whose aggregation is a characteristic hallmark of Parkinson's disease, can be followed at the molecular level using optical super-resolution microscopy. We have explored in particular the elongation of preformed α-synuclein fibrils; using two-color single-molecule localization microscopy we are able to provide conclusive evidence that the elongation proceeds from both ends of the fibril seeds. Furthermore, the technique reveals a large heterogeneity in the growth

SUBMITTER: Pinotsi D 

PROVIDER: S-EPMC3901574 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature