A pesticide and iPSC dopaminergic neuron screen identifies and classifies Parkinson-relevant pesticides.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 05 2023
16 05 2023
Historique:
received:
21
06
2022
accepted:
20
04
2023
medline:
18
5
2023
pubmed:
17
5
2023
entrez:
16
5
2023
Statut:
epublish
Résumé
Parkinson's disease (PD) is a complex neurodegenerative disease with etiology rooted in genetic vulnerability and environmental factors. Here we 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. We associate long-term exposure to 53 pesticides with PD and identify co-exposure profiles. We then employ a live-cell imaging screening paradigm exposing dopaminergic neurons to 39 PD-associated pesticides. We find that 10 pesticides are directly toxic to these neurons. Further, we analyze pesticides typically used in combinations in cotton farming, demonstrating that co-exposures result in greater toxicity than any single pesticide. We find trifluralin is a driver of toxicity to dopaminergic neurons and leads to mitochondrial dysfunction. Our paradigm may prove useful to mechanistically dissect pesticide exposures implicated in PD risk and guide agricultural policy.
Identifiants
pubmed: 37193692
doi: 10.1038/s41467-023-38215-z
pii: 10.1038/s41467-023-38215-z
pmc: PMC10188516
doi:
Substances chimiques
Pesticides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2803Subventions
Organisme : NHLBI NIH HHS
ID : F32 HL154644
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES010544
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL151684
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2023. The Author(s).
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