A versatile yeast model identifies the pesticides cymoxanil and metalaxyl as risk factors for synucleinopathies

• DOI: 10.1016/j.chemosphere.2024.143039
• Publication Date: 2024-08-06T06:36:32Z
• Authors: Leslie Amaral; Filipa Mendes; Manuela Côrte-Real; António Rego; Tiago F. Outeiro; Susana R. Chaves
• Keywords: Metalaxyl; Synucleinopathies

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and presence Lewy bodies, which predominantly consist aggregated forms protein alpha-synuclein (aSyn). While these aggregates are pathological hallmark PD, etiology most cases remains elusive. Although environmental risk factors have been identified, such as pesticides dieldrin MTPT, many others remain to be assessed their molecular impacts underexplored. This study aimed identify that could enhance aSyn aggregation using humanized yeast model expressing fused GFP primary screening platform, we validated dieldrin. We found cymoxanil metalaxyl induce in yeast, confirmed also occurs inclusion formation human H4 cells. In conclusion, our approach generated invaluable data on effect pesticides, therefore providing insights into mechanisms associated with onset progression PD other synucleinopathies.