A new study from UCLA Health reports that long-term exposure to the pesticide chlorpyrifos in residential areas is associated with a significantly increased risk of Parkinson’s disease. People living in areas with continuous exposure were more than 2.5 times more likely to develop the condition. Research published in journals molecular neurodegenerationcombines extensive human data with laboratory experiments showing how pesticides damage brain cells that produce dopamine. Taken together, these results provide biological evidence supporting an association between chlorpyrifos exposure and Parkinson’s disease.
Nearly 1 million people in the United States have Parkinson’s disease. Parkinson’s disease is a progressive neurological disease that causes tremors, muscle stiffness, and increased difficulty moving. Although genetics contribute in some cases, scientists now recognize that environmental exposures are also important risk factors. Pesticides have attracted particular attention in recent years.
Chlorpyrifos has been widely applied in agriculture for decades. Residential use was banned in 2001, and restrictions for agricultural use were introduced in 2021. Still, the chemical continues to be used on a variety of crops in the United States and continues to be commonly used in other parts of the world. Identifying specific pesticides that increase risk for Parkinson’s disease could guide prevention efforts and facilitate early monitoring and identification of individuals who may benefit from future protective therapies.
How researchers studied exposure to pesticides
To investigate the potential link, researchers looked at data from 829 people diagnosed with Parkinson’s disease and 824 people without Parkinson’s disease. All participants were participants in UCLA’s long-running Parkinson’s Disease Environment and Genetics Study.
The researchers combined California pesticide use records with the location of participants’ homes and workplaces to estimate each participant’s exposure to chlorpyrifos over time. This approach allowed scientists to reconstruct possible exposure patterns over many years.
The research team also conducted laboratory experiments to determine how pesticides damage the brain. Mice were exposed to aerosolized chlorpyrifos for 11 weeks through an inhalation method designed to mimic how humans typically encounter this chemical. Additional experiments in zebrafish were used to investigate the biological processes involved in injury.
Evidence of brain cell damage
Human data revealed that people with long-term residential exposure to chlorpyrifos had a more than 2.5 times higher risk of developing Parkinson’s disease than people with little or no exposure.
Test results showed similar red flags. Mice exposed to pesticides developed movement disorders and lost dopamine-producing neurons, the same type of brain cells that gradually die in Parkinson’s disease. The researchers also observed brain inflammation and abnormal accumulation of alpha-synuclein, a protein that forms clumps in the brains of Parkinson’s patients.
Experiments in zebrafish provided further clues. Studies have shown that chlorpyrifos disrupts autophagy, a cellular system that removes damaged proteins from cells. When researchers restored this purification process or removed the synuclein protein, neurons were protected from damage.
Potential future treatments
The finding that chlorpyrifos inhibits autophagy highlights a potential target for future treatments aimed at protecting the brain from pesticide-related damage. Scientists say that although chlorpyrifos use has declined in the United States, many people have had past exposure and similar insecticides are still widely used.
Future studies could investigate whether other commonly used pesticides affect the brain in similar ways. Scientists also want to determine whether treatments that enhance cells’ natural protein cleaning systems can lower the risk of Parkinson’s disease in exposed populations. This finding further suggests that individuals with known past exposure to chlorpyrifos may benefit from closer neurological monitoring.
Expert perspective
“This study demonstrates that chlorpyrifos, not just a common type of pesticide, is a specific environmental risk factor for Parkinson’s disease,” said Dr. Jeff Bronstein, professor of neurology at UCLA Health and lead author of the study. “By demonstrating the biological mechanism in an animal model, we demonstrated that this association is likely causal. The finding that autophagy dysfunction causes neurotoxicity also leads us to potential therapeutic strategies to protect vulnerable brain cells.”
