Summary
Summary: Parkinson's disease (PD) is a complex neurodegenerative disease with etiology rooted in genetic vulnerability and environmental factors. Authors combine quantitative epidemiologic study of pesticide exposures and PD with toxicity screening in dopaminergic neurons derived from PD patient induced pluripotent stem cells (iPSCs) to identify Parkinson's-relevant pesticides. Agricultural records enable investigation of 288 specific pesticides and PD risk in a comprehensive, pesticide-wide association study. Authors associate long-term exposure to 53 pesticides with PD and identify co-exposure profiles. Authors then employ a live-cell imaging screening paradigm exposing dopaminergic neurons to 39 PD-associated pesticides.
Findings: Authors find that 10 pesticides are directly toxic to these neurons. Further, they analyze pesticides typically used in combinations in cotton farming, demonstrating that co-exposures result in greater toxicity than any single pesticide. Authors find trifluralin is a driver of toxicity to dopaminergic neurons and leads to mitochondrial dysfunction. Their paradigm may prove useful to mechanistically dissect pesticide exposures implicated in PD risk and guide agricultural policy.
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