Studies have shown that certain pesticides can increase people’s risk of developing Parkinson’s disease. Now, UCLA researchers have found that the strength of the risk depends on an individual’s genetic makeup, which, in the most pesticide-exposed populations, could increase a person’s chance of developing the debilitating disease two-to-six fold.
|Illustration: David Blattel|
In an earlier study, the UCLA team discovered a link between Parkinson’s and the pesticide benomyl, a fungicide that has been banned by the U.S. Environmental Protection Agency. That study found that benomyl prevents the enzyme aldehyde dehydrogenase (ALDH) from converting aldehydes — organic compounds that are highly toxic to dopamine cells in the brain — into less-toxic agents, thereby contributing to the risk of Parkinson’s. For the current study, UCLA researchers tested a number of additional pesticides and found 11 that also inhibit ALDH and increase the risk of Parkinson’s — and at levels much lower than they are currently being used.
They also found that people with a common genetic variant of the ALDH2 gene are particularly sensitive to the effects of ALDHinhibiting pesticides and are two-to-six times more likely to develop Parkinson’s when exposed to these pesticides than those without the variant. “We were very surprised that so many pesticides inhibited ALDH and at quite low concentrations — concentrations that were way below what was needed for the pesticides to do their job,” says Jeff Bronstein, MD ’88 (RES ’92), PhD ’88, professor of neurology and director of the movement disorders program at UCLA. “These pesticides are pretty ubiquitous and can be found on our food supply. They are used in parks and golf courses and in pest control inside buildings and homes. So this significantly broadens the number of people at risk.” In the previous study, Dr. Bronstein and his team had determined the mechanism that leads to increased risk. Exposure to pesticides starts a cascade of cellular events, preventing ALDH from keeping a lid on the aldehyde DOPAL, a toxin that naturally occurs in the brain.
When ALDH does not detoxify DOPAL sufficiently, DOPAL accumulates, damages neurons and increases an individual’s risk of developing Parkinson’s. In the current study, the research team developed a lab test to determine which pesticides inhibited ALDH. They then found that those participants in the epidemiological study who had a genetic variant in the ALDH gene were at increased risk of Parkinson’s when exposed to these pesticides. The report suggests that therapies modulating ALDH enzyme activity or otherwise eliminating toxic aldehydes should be developed and tested to potentially reduce Parkinson’s disease occurrence or slow its progression, particularly for patients exposed to pesticides.
“Aldehyde dehydrogenase variation enhances effect of pesticides associated with Parkinson disease,” Neurology, February 4, 2014