Author(s):
Amaral, Leslie Ann Silva ; Mendes, Filipa ; Côrte-Real, Manuela ; Rego, António MIguel Araújo ; Outeiro, Tiago F. ; Chaves, Susana R.
Date: 2024
Persistent ID: https://hdl.handle.net/1822/92870
Origin: RepositóriUM - Universidade do Minho
Project/scholarship:
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04050%2F2020/PT;
info:eu-repo/grantAgreement/FCT/POR_NORTE/2020.05944.BD/PT;
info:eu-repo/grantAgreement/FCT/POR_NORTE/SFRH%2FBD%2F147574%2F2019/PT;
Subject(s): Parkinsons disease; Alpha-synuclein; Pesticides; Yeast; Environmental factors; Human neuroglioma cells
Description
Parkinson'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 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 onset and progression of PD and other synucleinopathies.
Investigation by the authors has been supported by national funds (Portuguese Science Foundation, FCT) via the institutional programs supporting CBMA (UIDB/04050/2020, DOI: 10.54499/UIDB/04050/2020) and ARNET (LA/P/0069/2020, DOI: 10.54499/LA/P/0069/2020), and funding to Susana Chaves DOI:10.54499/DL57/2016/ CP1377/CT0026. Leslie Amaral and Filipa Mendes were supported by individual doctoral grants (2020.05944.BD) and (SFRD/BD/147574/2019) by FCT. T.F.O. is supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy - EXC 2067/1-390729940, and by SFB1286(B8).
info:eu-repo/semantics/publishedVersion
