A pesticide used for decades in agriculture may be linked to a much higher risk of Parkinson’s disease, and scientists have discovered a possible explanation for how it damages the brain.
UCLA Health researchers found that people with long-term exposure to chlorpyrifos, a widely used pesticide, were more than 2.5 times more likely to develop Parkinson’s disease than those who were not exposed. Laboratory experiments also revealed how the chemical can interfere with the brain’s ability to clear damaged proteins, leading to the loss of nerve cells essential for controlling movement.
The study, published in Molecular neurodegenerationgoes beyond identifying a link between pesticide exposure and Parkinson’s disease. By examining what happens inside affected brain cells, researchers have discovered a biological mechanism that could potentially provide new ways to protect the brain from damage.
A common pesticide with a troubling link to Parkinson’s disease
Parkinson’s disease affects nearly a million Americans. The progressive neurological disease gradually damages the brain cells involved in movement, often causing tremors, muscle stiffness, slowing of movements and difficulty coordinating.
One of the defining features of Parkinson’s disease is the loss of neurons that produce dopamine. This chemical messenger allows nerve cells to communicate and helps the brain coordinate smooth, controlled movements. As dopamine levels decrease, the brain becomes less able to regulate these movements.
Although inherited genetic factors can influence the development of Parkinson’s disease, researchers are increasingly focusing on environmental exposures that may also contribute to the disease. Pesticides are of particular interest because some chemicals used to kill insects or other agricultural pests can also interfere with biological processes in the nervous system.
Chlorpyrifos has been widely used in agriculture for decades. Its residential use was banned in the United States in 2001, and its agricultural applications were subject to additional restrictions in 2021. However, the pesticide remains used on many crops in the United States and continues to be widely applied in other countries.
Because exposure may have occurred years before symptoms appeared, it is especially important to understand the potential long-term effects of chlorpyrifos. Identifying specific chemicals associated with Parkinson’s disease could help researchers develop prevention strategies and determine whether previously exposed people might benefit from additional neurological monitoring.
Researchers find risk of Parkinson’s disease more than doubles
To study this link, UCLA scientists examined information from 829 people diagnosed with Parkinson’s disease and 824 people without the condition. All participants were enrolled in the university’s long-term Parkinson’s Environment and Genes Study, which studies how environmental exposures and hereditary factors influence the risk of Parkinson’s disease.
The researchers combined detailed pesticide application records in California with participants’ residential and business addresses. This allowed them to estimate how much chlorpyrifos individuals might have encountered over time, based on where they lived and worked.
The results revealed a striking association. People who experienced prolonged residential exposure to chlorpyrifos had a more than 2.5 times higher risk of developing Parkinson’s disease than those who did not have such exposure.
Although this population analysis could not establish that the pesticide directly caused Parkinson’s disease, the researchers took a step further to determine whether chlorpyrifos could produce the types of brain damage seen in people with the disease.
How the pesticide damages brain cells
The team exposed mice to chlorpyrifos in aerosol form for 11 weeks. The inhalation approach was designed to resemble a common way people can encounter pesticides in the environment.
The exposed mice developed movement difficulties and lost the neurons responsible for dopamine production. This was particularly important because degeneration of these same nerve cells is a central feature of Parkinson’s disease.
The researchers also detected inflammation in the animals’ brains, as well as an abnormal accumulation of a protein called alpha-synuclein.
Under normal conditions, alpha-synuclein is found in nerve cells and plays a role in their function. However, the protein can accumulate in abnormal clumps closely associated with Parkinson’s disease. These deposits constitute a major area of research aimed at determining why certain brain cells gradually deteriorate.
Together, the results showed that exposure to chlorpyrifos could reproduce several important features of Parkinson’s disease in laboratory animals, strengthening the biological evidence behind the findings in the human population.
Scientists discover a breakdown in the brain’s cleaning system
The researchers then turned to zebrafish to study exactly how chlorpyrifos damages neurons. These small fish are frequently used in neuroscience research because they allow scientists to study the biological processes involved in the development and survival of nerve cells.
Their experiments showed disruption of autophagy, a natural cellular maintenance process that helps remove damaged proteins and other unwanted materials.
Autophagy works a bit like an internal recycling system. Cells use it to break down worn or defective components to prevent the buildup of potentially hazardous materials. This process is particularly important for neurons, many of which must remain functional throughout life.
When chlorpyrifos interfered with this cleaning system, damaged materials accumulated inside the neurons, contributing to their deterioration.
The researchers also made an encouraging discovery. When they restored the cell cleaning process or removed the protein synuclein in their experiments, the neurons were protected from damage.
This finding suggests that the harmful effects of the pesticide may depend in part on a biological pathway that researchers could potentially target with future treatments.
A potential new strategy to protect against Parkinson’s disease
This discovery opens the possibility of developing therapies that strengthen the brain’s cellular cleansing mechanisms and help protect vulnerable neurons. Such treatments could potentially prove useful for people exposed to chlorpyrifos or other pesticides that disrupt similar processes.
However, protective effects have so far been demonstrated in laboratory models. Further research will be needed to determine whether enhancing autophagy can prevent or reduce pesticide-related brain damage in humans.
Scientists also want to determine whether other commonly used pesticides interfere with the same cellular mechanisms. Although the use of chlorpyrifos has declined in the United States, many people were exposed to it before restrictions were introduced, and related agricultural chemicals remain widely used.
The findings could also help identify people with a history of significant pesticide exposure who might benefit from closer neurological monitoring. Earlier recognition of possible changes in brain function may become increasingly important as researchers work toward treatments that slow or prevent the progression of Parkinson’s disease.
Dr. Jeff Bronstein, professor of neurology at UCLA Health and lead author of the study, emphasized the importance of identifying a particular chemical rather than treating all pesticides as a single category.
“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.
“By showing the biological mechanism in animal models, we demonstrated that this association is likely causal. The discovery that autophagy dysfunction drives neurotoxicity also points us toward potential therapeutic strategies to protect vulnerable brain cells.”
Gn Health
