Browse by author
Lookup NU author(s): Professor Tiago OuteiroORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2024 The AuthorsParkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and the presence of Lewy bodies, which predominantly consist of aggregated forms of the protein alpha-synuclein (aSyn). While these aggregates are a pathological hallmark of PD, the etiology of most cases remains elusive. Although environmental risk factors have been identified, such as the pesticides dieldrin and MTPT, many others remain to be assessed and their molecular impacts are underexplored. This study aimed to identify pesticides that could enhance aSyn aggregation using a humanized yeast model expressing aSyn fused to GFP as a primary screening platform, which we validated using dieldrin. We found that the pesticides cymoxanil and metalaxyl induce aggregation of aSyn in yeast, which we confirmed also occurs in a model of aSyn inclusion formation using human H4 cells. In conclusion, our approach generated invaluable molecular data on the effect of pesticides, therefore providing insights into mechanisms associated with the onset and progression of PD and other synucleinopathies.
Author(s): Amaral L, Mendes F, Corte-Real M, Rego A, Outeiro TF, Chaves SR
Publication type: Article
Publication status: Published
Journal: Chemosphere
Year: 2024
Volume: 364
Print publication date: 01/09/2024
Online publication date: 06/08/2024
Acceptance date: 05/08/2024
Date deposited: 19/08/2024
ISSN (print): 0045-6535
ISSN (electronic): 1879-1298
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/j.chemosphere.2024.143039
DOI: 10.1016/j.chemosphere.2024.143039
Data Access Statement: Data will be made available on request.
PubMed id: 39117080
Altmetrics provided by Altmetric
