Effect of pyrimethanil on aβ42 aggregation mechanisms revealed at single entity level and molecular dynamic simulations
Abstract
This study investigated the impact of pyrimethanil, a fungicide, on the aggregation of amyloid-β 42 (aβ42) peptides in vitro. The findings demonstrated that pyrimethanil accelerated aβ42 aggregation kinetics, as evidenced by thioflavin T (ThT) fluorescence assays in both tube and microplate experiments. A combination of single molecule techniques and molecular dynamics simulations is used to elucidate the complex effects of pyrimethanil on aβ42 aggregation mechanism. Nanopore experiments indicated that pyrimethanil promoted the formation of small oligomers (6-13.5 nm) during the lag phase, which were not detected under control conditions. Confocal fluorescence spectroscopy revealed that pyrimethanil induced the formation of larger β-sheet structured aggregates. In the presence of preformed seeds, pyrimethanil exhibited a dual role by fragmenting existing fibrils into smaller species and enhancing aggregation, likely through combined effects with the newly formed smaller seeds. Molecular dynamics simulations confirmed that pyrimethanil has a higher affinity for fibrils than monomers and weakens monomer-fibril interactions. Overall, this study elucidates the complex effects of pyrimethanil on aβ42 aggregation, involving promotion of primary nucleation, fibril fragmentation, and modulation of monomer-fibril interactions. These findings provide important mechanistic insights into how environmental factors like pesticides may influence amyloid aggregation processes relevant to Alzheimer's disease.
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BibTeX
@article{meyer2026effect,
title = {{Effect of pyrimethanil on aβ42 aggregation mechanisms revealed at single entity level and molecular dynamic simulations}},
author = {Nathan Meyer and Nicolas Arroyo and Lois Roustan and Jean-Marc Janot and Véronique Perrier and Joan Torrent and Fabien Picaud and Sebastien Balme},
journal = {Biophysical Chemistry},
year = {2026},
month = sep,
doi = {10.1016/j.bpc.2025.107471},
url = {https://hal.umontpellier.fr/hal-05735840v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Effect of pyrimethanil on aβ42 aggregation mechanisms revealed at single entity level and molecular dynamic simulations
AU - Nathan Meyer
AU - Nicolas Arroyo
AU - Lois Roustan
AU - Jean-Marc Janot
AU - Véronique Perrier
AU - Joan Torrent
AU - Fabien Picaud
AU - Sebastien Balme
PY - 2026
DA - 2026/09/02
JO - Biophysical Chemistry
DO - 10.1016/j.bpc.2025.107471
UR - https://hal.umontpellier.fr/hal-05735840v1
AB - This study investigated the impact of pyrimethanil, a fungicide, on the aggregation of amyloid-β 42 (aβ42) peptides in vitro. The findings demonstrated that pyrimethanil accelerated aβ42 aggregation kinetics, as evidenced by thioflavin T (ThT) fluorescence assays in both tube and microplate experiments. A combination of single molecule techniques and molecular dynamics simulations is used to elucidate the complex effects of pyrimethanil on aβ42 aggregation mechanism. Nanopore experiments indicated that pyrimethanil promoted the formation of small oligomers (6-13.5 nm) during the lag phase, which were not detected under control conditions. Confocal fluorescence spectroscopy revealed that pyrimethanil induced the formation of larger β-sheet structured aggregates. In the presence of preformed seeds, pyrimethanil exhibited a dual role by fragmenting existing fibrils into smaller species and enhancing aggregation, likely through combined effects with the newly formed smaller seeds. Molecular dynamics simulations confirmed that pyrimethanil has a higher affinity for fibrils than monomers and weakens monomer-fibril interactions. Overall, this study elucidates the complex effects of pyrimethanil on aβ42 aggregation, involving promotion of primary nucleation, fibril fragmentation, and modulation of monomer-fibril interactions. These findings provide important mechanistic insights into how environmental factors like pesticides may influence amyloid aggregation processes relevant to Alzheimer's disease.
SN - 0301-4622
ER -