It is well known that certain Pesticides increase the risk of Parkinson’s disease. However, a new UCLA study has found that the degree of risk depends on an individual’s genetic makeup. Their findings may not only be useful for risk evaluation but also could lead to new therapies to treat the progressive neurological disease. The findings will appear on February 5 in the online issue of Neurology, the medical journal of the American Academy of Neurology.
About one year ago, in January 2013, the UCLA researchers published a study in the Proceedings of the National Academy of Sciences; they reported that they had discovered a link between Parkinson’s disease and the pesticide benomyl, which is a fungicide that has been banned by the US Environmental Protection Agency (EPA). That study reported that benomyl inhibited an enzyme known as aldehyde dehydrogenase (ALDH), which converts aldehydes highly toxic to dopamine cells into less toxic agents; thus, the pesticide increases the risk of developing Parkinson’s disease. The researchers determined the mechanism that leads to increased risk. Exposure to pesticides starts a cascade of cellular events, preventing ALDH from controlling the levels of DOPAL, which is a toxin that naturally occurs in the brain. When ALDH is ineffective in detoxifying DOPAL, it accumulates. As a result, neurons are damged and the risk of developing Parkinson’s disease increases.
The new study evaluated a variety of other pesticides and found 11, which also inhibit ALDH and increase the risk of Parkinson’s disease. Furthermore, these pesticides increased the risk at much lower levels than those that are currently contained in currently used pesticides.
Lead author Jeff Bronstein, a professor of neurology and director of movement disorders at UCLA, and his colleagues also found that individuals with a common genetic variant of the ALDH2 gene are particularly sensitive to the effects of ALDH-inhibiting pesticides; when exposed to these pesticides, these individuals are two to six times more likely to develop Parkinson’s disease 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,” explained Dr. Bronstein. He added, “These pesticides are pretty ubiquitous, and can be found on our food supply and 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.”
The researchers compared 360 patients with Parkinson’s disease in three agriculturally heavy Central California counties to 816 individuals from the same area who did not have Parkinson’s disease. They accessed data from the California Department of Pesticide Regulation and focused on individuals with regular exposures to pesticides at work and at home.
“ALDH inhibition appears to be an important mechanism by which these environmental toxins contribute to Parkinson’s pathogenesis, especially in genetically vulnerable individuals,” explained study author Beate Ritz, a professor of epidemiology at the Fielding School of Public Health at UCLA. She added, “This suggests several potential interventions to reduce Parkinson’s occurrence or to slow its progression.”
The researchers developed a laboratory test to determine which pesticides inhibited ALDH. Then, they discovered that those participants in the epidemiologic study with a genetic variant in the ALDH gene were at increased risk of Parkinson’s disease when exposed to these pesticides. Hover, the mere presence of the gene did not increase the risk of the disease. The study authors wrote: “This report provides evidence for the relevance of ALDH inhibition in Parkinson’s disease pathogenesis, identifies pesticides that should be avoided to reduce the risk of developing Parkinson’s disease and 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.”