Study shows how pesticides may contribute to development of Parkinson's disease

New research shows how pesticides may increase the risk of Parkinson's disease and that people with certain gene variants may be more susceptible to the disease. The research is published in the February 4, 2014, print issue of Neurology®, the medical journal of the American Academy of Neurology.

The research shows that certain pesticides that inhibit an enzyme called aldehyde dehydrogenase (ALDH) are related to an increased risk of Parkinson's disease. The enzyme plays a role in detoxifying substances in cells, along with metabolism of alcohol. The study also found that people with a variant of the ALDH2 gene were two to five times more likely to develop Parkinson's disease with exposure to these pesticides than people who did not have that gene variant.

"These results show that ALDH inhibition appears to be an important mechanism through which pesticides may contribute to the development of Parkinson's disease," said study author Jeff M. Bronstein, MD, PhD, of the David Geffen School of Medicine at UCLA and the Greater Los Angeles Veterans Affairs Medical Center and a member of the American Academy of Neurology. "Understanding this mechanism may reveal several potential targets for preventing the disease from occurring or reducing its progression."

The study involved 360 people with Parkinson's disease in three rural California counties who were compared to 816 people in the area who did not have the disease. Researchers looked at participants' exposure to pesticides at work and at home using a geographic computer model based on information from the California Department of Pesticide Regulation.

The researchers developed a test to identify which pesticides inhibited ALDH. The 11 pesticides that inhibited ALDH, all used in farming, fell into four structural classes—dithiocarbamates, imidazoles, dicarboxymides and organochlorides. Exposure to an ALDH-inhibiting pesticide at both the workplace and at home was associated with increased risks of developing Parkinson's disease, ranging from 65 percent for the pesticide benomyl to six times the risk for the pesticide dieldrin. People who were exposed to three or more of the pesticides at both work and home were 3.5 times more likely to develop Parkinson's disease as those who were not exposed.

Bronstein noted that the relationship between the gene variant and Parkinson's only appeared when people had been exposed to the pesticides. "In other words, having this gene variant alone does not make you more likely to develop Parkinson's," he said. "Parkinson's is a disease that in many cases may require both genetics and environmental factors to arise."

Bronstein said the findings provide several possible targets for lowering Parkinson's risk, including reducing exposure to pesticides and improving the functioning of ALDH.

The study was supported by the National Institute of Environmental Health Sciences, National Institute of Neurological Disorders and Stroke, Veterans Administration Healthcare System, Michael J. Fox Foundation, Levine Foundation and Parkinson Alliance.

Source: American Academy of Neurology

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