Insights Into Peptide Inhibition of Alpha-Synuclein Aggregation.

ABSTRACT: α-Synuclein (aSyn) aggregation is an attractive target for therapeutic development for a range of neurodegenerative conditions, collectively termed synucleinopathies. Here, we probe the mechanism of action of a peptide 4554W, (KDGIVNGVKA), previously identified through intracellular library screening, to prevent aSyn aggregation and associated toxicity. We utilize NMR to probe association and identify that 4554W associates with a "partially aggregated" form of aSyn, with enhanced association occurring over time. We also report the ability of 4554W to undergo modification through deamidation of the central asparagine residue, occurring on the same timescale as aSyn aggregation in vitro, with peptide modification enhancing its association with aSyn. Additionally, we report that 4554W

SUBMITTER: Torpey JH 

PROVIDER: S-EPMC7594713 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature