Conical nanopores highlight the pro-aggregating effects of pyrimethanil fungicide on Aβ(1–42) peptides and dimeric splitting phenomena - Université de Montpellier Accéder directement au contenu
Article Dans Une Revue Chemosphere Année : 2022

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

Résumé

The Aβ(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 Aβ(1-42) assembly and could influence the occurrence and pathophysiology of AD. However, pesticide involvement in the early stages of Aβ(1-42) aggregation is still unknown. Here, we employed conical track-etched nanopore in order to analyse the Aβ(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 Aβ(1-42). Aβ(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 Aβ(1-42) mechanism in two steps including the reorganization prior the elongation phase.

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Chimie
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Dates et versions

hal-03791236 , version 1 (29-09-2022)

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Nathan Meyer, Nicolas Arroyo, Matteo Baldelli, Nicolas Coquart, Jean-Marc Janot, et al.. Conical nanopores highlight the pro-aggregating effects of pyrimethanil fungicide on Aβ(1–42) peptides and dimeric splitting phenomena. Chemosphere, 2022, 291, pp.132733. ⟨10.1016/j.chemosphere.2021.132733⟩. ⟨hal-03791236⟩
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