A new study from UCLA Health has found that long-term residential exposure to the pesticide chlorpyrifos is associated with more than a 2.5-fold increased risk of developing Parkinson's disease. The research , published in the journal Molecular Neurodegeneration, combines human population data with laboratory experiments showing how the pesticide damages dopamine-producing brain cells, providing biological evidence for the link.
Why it matters
Nearly one million Americans live with Parkinson's disease, a progressive neurological disorder that causes tremors, stiffness and difficulty with movement. While genetics plays a role, environmental factors like pesticide exposure are increasingly recognized as important contributors. Chlorpyrifos has been widely used in agriculture for decades. Though its residential use was banned in 2001, and agricultural use was restricted in 2021, chlorpyrifos is still used on many crops in the US and widely used in other countries. Understanding which specific pesticides increase Parkinson's risk could inform prevention strategies and help identify people who may benefit from earlier monitoring or future protective treatments.
What the study did
Researchers analyzed data from 829 people with Parkinson's disease and 824 without the condition, all part of UCLA's long-running Parkinson's Environment and Genes study. The team used California's pesticide use reports along with participants' residential and work addresses to estimate individual exposure to chlorpyrifos over time. To understand how the pesticide might cause brain damage, researchers exposed mice to aerosolized chlorpyrifos for 11 weeks using inhalation methods that mimic how humans typically encounter the chemical. They also conducted experiments in zebrafish to identify the specific biological mechanisms of damage.
What they found
People with long-term residential chlorpyrifos exposure had more than 2.5 times the risk of developing Parkinson's disease compared to those without such exposure. Mice exposed to the pesticide developed movement problems and lost dopamine-producing neurons, the same cells that die in Parkinson's patients. The exposed mice also showed brain inflammation and abnormal accumulation of alpha-synuclein, a protein that clumps in Parkinson's disease. Zebrafish experiments revealed that chlorpyrifos damages neurons by disrupting autophagy, the cellular process that clears damaged proteins. When researchers restored this cleanup process or removed synuclein protein, the neurons were protected from damage.
What's next
The findings identify autophagy dysfunction as a potential target for developing treatments that could protect the brain from pesticide damage. Researchers note that while chlorpyrifos use has been reduced in recent years in the US, many people were exposed in the past and similar pesticides are still used widely. Future studies could examine whether other commonly used pesticides cause similar damage and whether interventions that enhance cellular cleanup processes might reduce Parkinson's risk in exposed populations. The work also suggests that people with known historical exposure to chlorpyrifos might benefit from closer neurological monitoring.
From the experts
"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."
