Summary: Researchers have identified 10 pesticides that directly damage the dopamine-producing neurons most affected in Parkinson’s disease, and found that common combinations used in cotton farming can be even more harmful than individual chemicals.
Using California’s comprehensive pesticide use records combined with laboratory toxicity screening, teams from UCLA Health and Harvard pinpointed specific chemicals that harm dopaminergic neurons—cells essential for voluntary movement whose loss is a hallmark of Parkinson’s disease. The study highlights both individual agents and real-world mixtures that may contribute to disease risk.
Key facts
- Ten pesticides were shown to be directly toxic to dopaminergic neurons, the cells central to motor control and Parkinson’s pathology.
- Mixtures of pesticides commonly applied together in cotton agriculture caused greater toxicity than single pesticides alone.
- Most of the identified pesticides remain in use today in the United States, underscoring potential ongoing exposure concerns.
Source: UCLA
Overview
UCLA Health and Harvard researchers combined large-scale epidemiologic data with cellular toxicity testing to investigate which pesticides are most relevant to Parkinson’s disease. While past studies have linked pesticide exposure generally to increased Parkinson’s risk, this work narrows the focus to specific chemicals and to combinations used in contemporary agriculture.
California, the nation’s largest agricultural producer, maintains a detailed pesticide use database that catalogues thousands of products and active ingredients. The investigators leveraged these records to reconstruct long-term exposure histories for people in the Central Valley who participated in previous Parkinson’s studies. That exposure reconstruction covered 288 distinct pesticides and enabled an agnostic, pesticide-wide association analysis to detect agents linked to Parkinson’s.
From the epidemiologic screen, 53 pesticides emerged as associated with Parkinson’s disease. Those candidates were then evaluated in lab experiments led by Richard Krolewski, MD, PhD, at Harvard and Brigham and Women’s Hospital. Using induced pluripotent stem cells (iPSCs) derived from Parkinson’s patients, the team reprogrammed cells into dopaminergic neurons—cells that closely resemble those lost in Parkinson’s—and tested pesticide toxicity with live-cell imaging.
Ten pesticides produced direct toxicity in these patient-derived dopaminergic neurons. They include four insecticides (dicofol, endosulfan, naled, propargite), three herbicides (diquat, endothall, trifluralin), and three fungicides (basic and pentahydrate copper sulfate, and folpet). The identified chemicals span different classes, structures, and prior toxicity classifications, suggesting that diverse mechanisms may underlie their effects on dopamine neurons.
Importantly, the researchers tested pesticide mixtures that reflect common co-application patterns in cotton fields. Combinations that included trifluralin—a widely used herbicide in California—showed especially high toxicity. Previous epidemiologic research, including the Agricultural Health Study, had already implicated trifluralin in Parkinson’s, and the laboratory findings here point to mitochondrial dysfunction as one pathway by which it harms dopaminergic neurons.
Implications and next steps
This field-to-bench approach—linking population exposure data with patient-derived cell models—provides a scalable way to prioritize pesticides for further mechanistic study and regulatory consideration. The team plans to expand analyses using integrative omics to examine epigenetic and metabolomic changes associated with pesticide exposure, aiming to identify the biological pathways disrupted in exposed patients.
Additional laboratory work at Harvard and Brigham and Women’s labs will investigate specific neuronal processes affected by key pesticides such as trifluralin and copper compounds. Those studies will explore impacts on both dopamine neurons, which drive the movement symptoms of Parkinson’s, and cortical neurons, which contribute to cognitive symptoms. Researchers will also examine effects on glial cells to better understand how pesticides influence non-neuronal brain cells that support neuronal health and function.
By combining comprehensive exposure assessment with patient-relevant cell models, this research narrows the list of suspect pesticides and clarifies which agents and real-world mixtures deserve priority for regulation, monitoring, and deeper mechanistic investigation in the context of Parkinson’s disease risk.
Other contributors to the study include Edinson Lucumi Moreno, Jack Blank, Kristina M. Holton, Tim Ahfeldt, Melissa Furlong, Yu Yu, Myles Cockburn, Laura K. Thompson, Alexander Kreymerman, Elisabeth M. Ricci-Blair, Yu Jun Li, Heer B. Patel, Richard T. Lee, Jeff Bronstein, Lee L. Rubin, Vikram Khurana, and Beate Ritz.
About this Parkinson’s disease research news
Author: Jason Millman
Source: UCLA
Contact: Jason Millman – UCLA
Image: The image is credited to Neuroscience News
Original research: Open access. “A pesticide and iPSC dopaminergic neuron screen identifies and classifies Parkinson-relevant pesticides” by Richard Krolewski et al., published in Nature Communications.
Abstract
A pesticide and iPSC dopaminergic neuron screen identifies and classifies Parkinson-relevant pesticides
Parkinson’s disease is a multifactorial neurodegenerative disorder influenced by genetic susceptibility and environmental exposures. This study integrates quantitative epidemiology of agricultural pesticide exposures with toxicity screening in dopaminergic neurons derived from PD patient iPSCs to identify pesticides relevant to Parkinson’s disease.
Using agricultural records, the investigators assessed long-term exposure to 288 specific pesticides in a comprehensive pesticide-wide association study and linked 53 pesticides to Parkinson’s disease, identifying common co-exposure profiles. A live-cell imaging screen of 39 PD-associated pesticides in patient-derived dopaminergic neurons revealed 10 pesticides that directly impair these neurons. Co-exposures typical of cotton farming produced greater toxicity than single agents, with trifluralin identified as a significant driver of mitochondrial dysfunction in dopaminergic cells. This combined paradigm can help dissect mechanisms by which pesticide exposures contribute to PD risk and may inform agricultural policy and targeted follow-up research.