Nearly one million people in the United States are living with Parkinson’s disease, a progressive neurological disorder that causes tremors, muscle stiffness, and increasing difficulty with movement. Although genetics contributes to some cases, scientists now recognize environmental exposures as important risk factors as well. Pesticides have drawn particular attention in recent years.

Chlorpyrifos has been widely applied in agriculture for decades. Its residential use was banned in 2001, and restrictions on agricultural applications were introduced in 2021. Even so, the chemical continues to be used on a variety of crops in the US and remains common in other parts of the world. Identifying specific pesticides that increase Parkinson’s risk could help guide prevention efforts and make it easier to identify individuals who might benefit from earlier monitoring or future protective therapies.

How Researchers Studied Pesticide Exposure

To investigate the potential link, researchers examined data from 829 people diagnosed with Parkinson’s disease and 824 individuals without the condition. All participants were part of UCLA’s long-running Parkinson’s Environment and Genes study.

The research team estimated each participant’s exposure to chlorpyrifos over time by combining California pesticide use records with the locations of participants’ homes and workplaces. This approach allowed scientists to reconstruct likely exposure patterns across many years.

To explore how the pesticide might damage the brain, the team also conducted laboratory experiments. Mice were exposed to aerosolized chlorpyrifos for 11 weeks through inhalation methods designed to mimic how people typically encounter the chemical. Additional experiments in zebrafish were used to investigate the biological processes involved in the damage.

Evidence of Brain Cell Damage

The human data revealed that individuals with long-term residential exposure to chlorpyrifos had more than a 2.5 times greater risk of developing Parkinson’s disease compared with those who had little or no exposure.

The laboratory results showed similar warning signs. Mice exposed to the pesticide developed movement problems and lost dopamine-producing neurons, the same type of brain cells that gradually die in Parkinson’s disease. Researchers also observed brain inflammation and an abnormal buildup of alpha-synuclein, a protein that forms clumps in the brains of people with Parkinson’s.

Experiments in zebrafish offered additional clues. The studies showed that chlorpyrifos disrupts autophagy, the cellular system responsible for clearing damaged proteins from cells. When researchers restored this cleanup process or removed synuclein protein, the neurons were protected from injury.

Potential Paths for Future Treatments

The discovery that chlorpyrifos interferes with autophagy highlights a possible target for future therapies aimed at protecting the brain from pesticide-related damage. Scientists say that although chlorpyrifos use has declined in the US, many people experienced exposure in the past and similar pesticides are still widely used.

Future research may examine whether other commonly used pesticides affect the brain in similar ways. Scientists also hope to determine whether treatments that enhance the cell’s natural protein cleanup systems could lower Parkinson’s risk in exposed populations. The findings further suggest that individuals known to have had past exposure to chlorpyrifos might benefit from closer neurological monitoring.

Expert Perspective

“This study establishes chlorpyrifos as a specific environmental risk factor for Parkinson’s disease, not just pesticides as a general class,” said Dr. Jeff Bronstein, professor of Neurology at UCLA Health and the study’s senior author. “By showing the biological mechanism in animal models, we’ve demonstrated that this association is likely causal. The discovery that autophagy dysfunction drives the neurotoxicity also points us toward potential therapeutic strategies to protect vulnerable brain cells.”