(Beyond Pesticides, January 8, 2013) Neurologists at the University of California, Los Angeles (UCLA) have published their latest research linking pesticide exposure to Parkinsonâ€™s disease. Appearing in the online edition of PNAS, the UCLA scientistsâ€™ work details the series of events that can occur after individuals are exposed to the pesticide benomyl, which was phased out in 2001. Researchers believe their findings on the series of events the pesticide sets in motion could be applicable even to Parkinsonâ€™s patients who have not been exposed to benomyl.
According to scientists, exposure to benomyl prevents the enzyme aldehyde dehydrogenase (ALDH) from keeping in check a naturally occurring toxin in the brain called 3,4-Dihydroxyphenylacetaldehyde (DOPAL). Without ALDH regulating DOPAL, the toxin accumulates, damages neurons, and increases an individualâ€™s risk of developing Parkinsonâ€™s disease. Researchers postulate that this process may be occurring in people with Parkinsonâ€™s who were never exposed to pesticides. The findings of this research provide insight into possible treatments to slow the disease, such as developing new drugs to protect ALDH activity.
Although the exact cause of Parkinsonâ€™s is still unknown, until this research scientists were focusing in on the protein a-synuclein as a pathway to the disease. The protein, present in all Parkinsonâ€™s patients, is thought to create the conditions for Parkinsonâ€™s when it binds together and becomes toxic, killing neurons in the brain.
Parkinsonâ€™s is the second most common neurodegenerative disease, affecting one to two percent of people over the age of 65. Parkinsonâ€™s disease occurs when nerve cells in the substantia nigra region of the brain are damaged or destroyed and can no longer produce dopamine, a nerve-signaling molecule that helps control muscle movement. Often by the time Parkinson’s symptoms manifest themselves, more than half of these molecules, known as dopaminergic neurons, have already been lost.
People with Parkinsonâ€™s have a variety of symptoms, including loss of muscle control, temors, sluggish movement, muscle stiffness, and lack of coordination. They may also experience anxiety, constipation, dementia, depression, urinary difficulties, and sleep disturbances. Over time, symptoms intensify. At least one million Americans have Parkinsonâ€™s and about 50,000 new cases are diagnosed each year. Although medical treatments may improve symptoms, there are none that can slow down or halt the progression of the disease.
While certain genetic variations may cause an inherited form of Parkinsonâ€™s, lead author of the study Arthur G Fitzmaurice, Ph.D.Â notes that that only a small fraction of the disease can be blamed on genes. “As a result, environmental factors almost certainly play an important role in this disorder. Understanding the relevant mechanisms â€” particularly what causes the selective loss of dopaminergic neurons â€” may provide important clues to explain how the disease develops,” Dr. Fitzmaurice explains.
Pesticides are long suspected of being tied to Parkinsonâ€™s, at least in part, because of the high rate of the disease among farmworkers. Farmworkers have nearly double the risk for the disease if exposed to pesticides, with a dose-effect for the number of years of exposure. However, even individuals who simply lived near agricultural fields are at risk. Exposure to the pesticides, paraquat and maneb, within 500 meters of an individualâ€™s home, has been shown to increase the risk of developing Parkinsonâ€™s by 75 percent, according to a University of California, Berkeley study. The Institute of Medicine (IOM) found suggestive but limited evidence that exposure to Agent Orange and other herbicides used during the Vietnam War is associated with an increased chance of developing ischemic heart disease and Parkinsonâ€™s disease in Vietnam veterans. Another publication found that rural residents who drank contaminated well water had an increased (up to 90 percent) risk of developing Parkinsonâ€™s. French researchers also found that among men exposed to pesticides such as DDT, carriers of the gene variants are three and a half times more likely to develop Parkinsonâ€™s than those with the more common version of the gene.
Last year, researchers at the University of Missouri School of Medicine took some of the first steps toward understanding the link between pesticides and Parkinsonâ€™s, and unraveling the molecular dysfunction that occurs when proteins are exposed to environmental toxicants. UCLAâ€™s earlier research, published in November 2012 found that exposure to pesticides and suffering a head injury are associated with a three-fold increase in oneâ€™s chances of developing Parkinsonâ€™s disease.
Senior author of the new study Jeff Bronstein, M.D., Ph.D.Â notes, “We’ve known that in animal models and cell cultures, agricultural pesticides trigger a neurodegenerative process that leads to Parkinson’s. And epidemiologic studies have consistently shown the disease occurs at high rates among farmers and in rural populations. Our work reinforces the hypothesis that pesticides may be partially responsible, and the discovery of this new pathway may be a new avenue for developing therapeutic drugs.”
Registrants of the pesticide benomyl voluntarily cancelled their Environmental Protection Agency (EPA) registration in 2001, with all sales and distribution of benomyl products ending in 2002. Both benomyl and its primary metabolite carbendazim (MBC) (which was illegally found in incoming shipments of orange juice from Brazil to the U.S. early last year) are of toxicological concern. Studies show benomyl and MBC to be teratogenic (causing birth defects), and both are considered possible human carcinogens by EPA.
Studies like these demonstrate the long-lasting toxicological effects that can result from pesticide use, even after the chemical has been removed from the marketplace. A 2006 study linked low-level but still environmentally relevant levels of the pesticide dieldrin, banned in 1987, to the onset of Parkinsonâ€™s disease. Dieldrin still exists in the environment, and was discovered as recently as July of last year at levels above what EPA considers acceptable in the private wells of many Connecticut residents. For additional information on how EPA ignores toxic exposures in its risk assessment process for approving pesticides, see Beyond Pesticidesâ€™ article Taking Off the Blindfold published in the Winter 2006 issue of Pesticides and You.
For more information on the latest research linking pesticides and Parkinsonâ€™s disease, see Beyond Pesticidesâ€™ Pesticide Induced Diseases Database (PIDD), or read the Parkinson’s Disease article from the Spring 2008 issue of Pesticides and You.
Source: UCLA Newsroom
All unattributed positions and opinions in this piece are those of Beyond Pesticides.