What the study found
Researchers at UCLA Health report that people with long-term residential exposure to chlorpyrifos, a widely used pesticide, had more than 2.5 times the risk of developing Parkinson's disease compared with people who were not exposed. The work was published in Molecular Neurodegeneration, according to Science Daily.
The team also ran laboratory experiments aimed at explaining how the chemical might damage the brain. They found that chlorpyrifos can interfere with the brain's ability to clear damaged proteins, which led to the loss of nerve cells that are essential for controlling movement.
How the research was done
The scientists drew on data from 829 people with Parkinson's disease and 824 people without it. All were enrolled in UCLA's long-running Parkinson's Environment and Genes study, which examines how environmental exposures and inherited factors affect risk. The team combined California's detailed pesticide application records with each participant's residential and workplace address histories to estimate exposure over time.
Because that kind of population analysis cannot show that a pesticide directly causes disease, the researchers moved to animal models. Mice were exposed to chlorpyrifos in aerosol form for 11 weeks, an approach meant to resemble a common route of environmental exposure. The animals developed movement difficulties and lost dopamine-producing neurons, a central feature of Parkinson's. The researchers also detected brain inflammation and abnormal clumps of alpha-synuclein, a protein closely associated with the disease.
A breakdown in the brain's cleanup system
To pinpoint how chlorpyrifos harms neurons, the team turned to zebrafish, which are frequently used in neuroscience research. Those experiments pointed to a disruption in autophagy, a natural maintenance process that works like an internal recycling system, breaking down worn-out or defective cell components. It is especially important for neurons, many of which must function throughout a person's lifetime.
When chlorpyrifos disrupted this process, damaged material built up inside neurons and contributed to their deterioration. When the researchers restored the cleanup process or removed synuclein protein in their experiments, the neurons were protected from damage. That suggests the pesticide's harmful effects depend partly on a pathway that future treatments might target.
Background and what comes next
Parkinson's disease affects nearly one million Americans, according to the report. It gradually damages cells involved in movement, often causing tremors, muscle stiffness, slowed movement and coordination problems. Chlorpyrifos has been used extensively in agriculture for decades. Its residential use was banned in the United States in 2001, and agricultural applications faced additional restrictions in 2021, but it remains in use on many U.S. crops and is widely applied in other countries.
The protective effects have so far been shown only in laboratory models, and more research is needed to learn whether strengthening autophagy could prevent or reduce pesticide-related brain damage in people. Scientists also want to test whether other commonly used pesticides affect the same cellular mechanisms. The findings could also help identify people with substantial past exposure who might benefit from closer neurological monitoring.
Dr. Jeff Bronstein, a professor of neurology at UCLA Health and the study's senior author, said, "This study establishes chlorpyrifos as a specific environmental risk factor for Parkinson's disease, not just pesticides as a general class." He added, "By showing the biological mechanism in animal models, we've demonstrated that this association is likely causal."
