2022 · CHEMOSPHERE

Conical nanopores highlight the pro-aggregating effects of pyrimethanil fungicide on Aβ(1-42) peptides and dimeric splitting phenomena

Meyer, Nathan, Arroyo, Nicolas, Baldelli, Matteo, Coquart, Nicolas, Janot, Jean Marc, Perrier, Veronique, Chinappi, Mauro, Picaud, Fabien, Torrent, Joan, Balme, Sebastien

Journal
CHEMOSPHERE
Année
2022
Volume
291
Numéro
1
Article
132733
Mois
MAR
DOI
10.1016/j.chemosphere.2021.132733

Abstract

The A beta(1-42) aggregation is a key event in the physiopathology of Alzheimer's disease (AD). Exogenous factors such as environmental pollutants, and more particularly pesticides, can corrupt A beta(1-42) assembly and could influence the occurrence and pathophysiology of AD. However, pesticide involvement in the early stages of A beta (1-42) aggregation is still unknown. Here, we employed conical track-etched nanopore in order to analyse the A beta (1-42) fibril formation in the presence of pyrimethanil, a widely used fungicide belonging to the anilinopyrimidine class. Our results evidenced a pro-aggregating effect of pyrimethanil on A beta(1-42). A beta(1-42) assemblies were successfully detected using conical nanopore coated with PEG. Using an analytical model, the large current blockades observed (>0.7) were assigned to species with size close to the sensing pore. The long dwell times (hundreds ms scale) were interpreted by the possible interactions amyloid/PEG using molecular dynamic simulation. Such interaction could leave until splitting phenomena of the dimer structure. Our work also evidences that the pyrimethanil induce an aggregation of A beta(1-42) mechanism in two steps including the reorganization prior the elongation phase.

Lire l'article complet