Modulation of the extent of structural heterogeneity in α-synuclein fibrils by the small molecule thioflavin T.

ABSTRACT: The transition of intrinsically disordered, monomeric α-synuclein into β-sheet-rich oligomers and fibrils is associated with multiple neurodegenerative diseases. Fibrillar aggregates possessing distinct structures that differ in toxicity have been observed in different pathological phenotypes. Understanding the mechanism of the formation of various fibril polymorphs with differing cytotoxic effects is essential for determining how the aggregation reaction could be modulated to favor nontoxic fibrils over toxic fibrils. In this study, two morphologically different α-synuclein fibrils, one helical and the other ribbon-like, are shown to form together. Surprisingly, a widely used small molecule for probing aggregation reactions, thioflavin T (ThT), was found to tune the structural heterogenei

SUBMITTER: Kumar H 

PROVIDER: S-EPMC5641877 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature