1. Conical nanopores highlight the pro-aggregating effects of pyrimethanil fungicide on Aβ(1-42) peptides and dimeric splitting phenomena
- Author
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Sebastien Balme, Fabien Picaud, Joan Torrent, Nathan Meyer, Jean-Marc Janot, Matteo Baldelli, Mauro Chinappi, Nicolas Arroyo, Véronique Perrier, Nicolas Coquart, Institut Européen des membranes (IEM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Université de Montpellier (UM), Nanomédecine, imagerie, thérapeutique - UFC (UR 4662) (NIT / NANOMEDECINE), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Università degli Studi di Roma Tor Vergata [Roma], Agro-Biotechnologies Industrielles (ABI), AgroParisTech, Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and FALQUE, Philippe
- Subjects
Environmental Engineering ,Amyloid ,Health, Toxicology and Mutagenesis ,Dimer ,Settore ING-IND/06 ,track-etched ,Molecular dynamics ,chemistry.chemical_compound ,Nanopores ,Fibril formation ,PEG ratio ,[CHIM] Chemical Sciences ,fungicide ,Environmental Chemistry ,[CHIM]Chemical Sciences ,nanopore ,Amyloid beta-Peptides ,Chemistry ,Public Health, Environmental and Occupational Health ,amyloid ,General Medicine ,General Chemistry ,Pollution ,resistive pulse ,Peptide Fragments ,Aβ(1-42) ,Fungicides, Industrial ,Nanopore ,Pyrimidines ,Aβ(1–42) ,Biophysics ,lag phase ,Pyrimethanil - Abstract
International audience; 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.
- Published
- 2021