Single-Molecule Characterization of the Interactions between Extracellular Chaperones and Toxic α-Synuclein Oligomers.

ABSTRACT: The aberrant aggregation of α-synuclein is associated with several human diseases, collectively termed the α-synucleinopathies, which includes Parkinson's disease. The progression of these diseases is, in part, mediated by extracellular α-synuclein oligomers that may exert effects through several mechanisms, including prion-like transfer, direct cytotoxicity, and pro-inflammatory actions. In this study, we show that two abundant extracellular chaperones, clusterin and α₂-macroglobulin, directly bind to exposed hydrophobic regions on the surface of α-synuclein oligomers. Using single-molecule fluorescence techniques, we found that clusterin, unlike α₂-macroglobulin, exhibits differential binding to α-synuclein oligomers that may be related to structural differences bet

SUBMITTER: Whiten DR 

PROVIDER: S-EPMC6024880 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature