Widely used pesticides may pose a greater threat to brain health than previously realized. UCLA Health researchers report that long-term exposure to chlorpyrifos near the home is associated with a more than 2.5-fold increased risk of developing Parkinson’s disease.
This research molecular neurodegenerationcombined evidence from hundreds of people with laboratory experiments designed to reveal exactly how pesticides affect the brain. The results suggest that chlorpyrifos can damage important nerve cells involved in movement and may play a direct role in the development of Parkinson’s disease.
Why is Parkinson’s disease important?
Parkinson’s disease is a progressive neurological disease that affects approximately 1 million Americans. This condition occurs when specialized brain cells that produce dopamine gradually die. Dopamine is a chemical messenger that helps control movement, coordination, and balance.
When dopamine levels drop, symptoms can include tremors, muscle stiffness, slowed movements, and difficulty maintaining balance. Although certain genetic factors may increase risk, researchers are increasingly focusing on environmental exposures that may contribute to the disease.
Pesticides have emerged as one of the major environmental problems. Scientists have long suspected that some chemicals used in agriculture can harm the nervous system, but it has been difficult to identify specific pesticides and understand how they affect the brain.
Chlorpyrifos remains widely used
Chlorpyrifos has been used in agricultural crops for decades. Although residential use of this pesticide was banned in 2001 and agricultural uses faced restrictions in 2021, the chemical continues to be used on a variety of crops in the United States and remains common in many other countries.
Because exposure can occur over many years, researchers are interested in understanding whether people who lived near treated fields may face long-term health effects.
Tracking exposure and Parkinson’s disease risk
To investigate this association, researchers analyzed data from 829 people diagnosed with Parkinson’s disease and 824 people without Parkinson’s disease. All participants were enrolled in the ongoing Parkinson’s Disease Environmental and Genetic Study at UCLA.
The research team combined California pesticide use records with residential and work addresses to estimate each participant’s long-term exposure to chlorpyrifos. This allowed researchers to determine who was likely to experience more exposure over time.
The results revealed a striking pattern. People with long-term residential exposure to chlorpyrifos had a more than 2.5 times higher risk of developing Parkinson’s disease than people who were not exposed.
Effects of pesticides on the brain
To better understand why this increased risk occurs, researchers conducted a series of laboratory experiments.
Mice were exposed to aerosolized chlorpyrifos for 11 weeks using an inhalation method designed to mimic how humans typically encounter pesticides in the environment. The exposed animals developed movement disorders and lost dopamine-producing neurons, the same type of brain cells that degenerate in Parkinson’s disease.
The researchers also observed signs of inflammation in the brain and abnormal accumulation of alpha-synuclein, a protein strongly associated with Parkinson’s disease. In patients with this disorder, alpha-synuclein can aggregate and interfere with normal brain function.
Collapse of the brain purification system
Additional experiments in zebrafish helped uncover the biological mechanisms behind the damage.
Researchers found that chlorpyrifos interferes with a process known as autophagy. Autophagy is often described as a cell’s internal cleaning and recycling system, removing damaged proteins and cellular debris before they can accumulate and cause harm.
When this purification process is disrupted, neurons become more susceptible to damage. But when the scientists restored autophagy or removed the synuclein protein, the nerve cells were protected from damage.
These results suggest that the pesticide may contribute to Parkinson’s disease by preventing cells from removing harmful substances and allowing toxic proteins to accumulate over time.
what happens next
This finding highlights autophagy as a potential target for future therapies aimed at protecting the brain from pesticide-related injuries.
Researchers note that although chlorpyrifos use has declined in recent years in the United States, many people experienced exposure before restrictions were put in place. Additionally, similar pesticides continue to be used around the world.
Future research will investigate whether other commonly used pesticides disrupt autophagy as well, and whether treatments that enhance the cell’s natural purification system could reduce the risk of Parkinson’s disease in exposed individuals.
The findings also suggest that people with known past exposure to chlorpyrifos may benefit from closer neurological monitoring, especially as researchers continue to investigate the long-term effects of pesticide exposure on brain health.
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.”
