Researchers at UCLA Health found that people with long-term residential exposure to chlorpyrifos had more than 2.5 times the risk of developing Parkinson's disease compared with those who were not exposed. The study, published in Molecular Neurodegeneration, examined 829 people with Parkinson's disease and 824 without the condition from UCLA's Parkinson's Environment and Genes study. Researchers combined California's pesticide application records with participants' residential and workplace histories to estimate exposure levels.
In laboratory experiments, the team exposed mice to chlorpyrifos aerosol for 11 weeks. The animals developed movement difficulties and lost dopamine-producing neurons, a central feature of Parkinson's disease. The researchers also detected brain inflammation and abnormal accumulations of alpha-synuclein protein in the exposed mice.
To investigate the mechanism of harm, researchers used zebrafish and found that chlorpyrifos disrupts autophagy, a cellular process that removes damaged proteins and waste material. When chlorpyrifos interfered with this cleanup system, harmful material accumulated inside neurons. However, when researchers restored the cleanup process or removed synuclein protein in experiments, neurons were protected from damage.
Dr. Jeff Bronstein, professor of Neurology at UCLA Health and senior author, stated, "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."
Chlorpyrifos residential use was banned in the United States in 2001, with agricultural restrictions added in 2021. The pesticide remains widely used on many crops in the U.S. and continues to be applied internationally. Researchers note that additional studies are needed to determine whether enhancing autophagy can prevent pesticide-related brain damage in humans.