Mechanistic Insights into Polyphenols' Aggregation Inhibition of α-Synuclein and Related Peptides.

ABSTRACT: While several polyphenols were found to either inhibit or modulate the aggregation of proteins implicated in neurodegenerative diseases, such as Parkinson's disease (PD), discrepant action mechanisms have been reported. This, in addition to some polyphenols' pan-assay interference compounds' reputation, casts some doubts concerning their therapeutic relevance. Here, we studied, through molecular dynamics and enhanced sampling methods, the aggregation of 11-mer peptides from the non-amyloid-β component, an aggregation-prone domain of α-synuclein (α-syn) implicated in PD and other synucleinopathies, in neat water and aqueous solutions of resveratrol (RSV) and gallic acid (GA). Further, simulations of the complete protein were carried out in aqueous urea, RSV, and GA solutions. Our results sh

SUBMITTER: Martins GF 

PROVIDER: S-EPMC10197135 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature