Long-term exposure to chlorpyrifos, a pesticide used extensively in agriculture for decades, was associated with more than 2.5 times the risk of Parkinson’s disease in a study by researchers at UCLA Health. Laboratory experiments also indicated how the chemical may damage brain cells and pointed to a possible protective strategy.
The researchers analyzed data from 829 people diagnosed with Parkinson’s disease and 824 people without the condition. By combining participants’ residential and workplace histories with California pesticide application records, they estimated long-term exposure to chlorpyrifos.
People with prolonged residential exposure had more than 2.5 times the risk of Parkinson’s compared with those without the recorded exposure. The population study identified an association and could not by itself prove that chlorpyrifos directly caused the disease.
To investigate the biological evidence, the team exposed mice to chlorpyrifos in aerosol form for 11 weeks. The animals developed movement problems, lost dopamine-producing neurons and showed signs of brain inflammation. Researchers also detected abnormal accumulations of alpha-synuclein, a protein closely associated with Parkinson’s disease when it forms harmful clumps.
Further experiments in zebrafish indicated that chlorpyrifos interferes with autophagy, the cellular process that removes damaged proteins and other unwanted material. Disruption of this internal cleanup system caused damaged material to accumulate in neurons and contributed to their deterioration.
The researchers reported that restoring the cleanup process or removing synuclein protein protected neurons in their experiments. The finding suggests that treatments aimed at strengthening autophagy could eventually help protect brain cells, although the effect has so far been demonstrated only in laboratory models.
The study, published in Molecular Neurodegeneration, also highlights the potential long-term relevance of past exposure. Residential use of chlorpyrifos was banned in the United States in 2001, while agricultural applications faced additional restrictions in 2021, but the pesticide remains used on some crops in the country and in other countries.
Dr. Jeff Bronstein, professor of Neurology at UCLA Health and the study’s senior author, said the findings identify chlorpyrifos as a specific environmental risk factor rather than treating pesticides as a single category. He added that the evidence linking autophagy dysfunction to neurotoxicity could guide future strategies to protect vulnerable neurons.
Sources: ScienceDaily.