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Researchers Establish Link Between Pesticides and Parkinson’s Disease

Study suggests potential new target for therapeutic drugs (Jan. 3)

For several years, neurologists at the University of California—Los Angeles have been building a case that a link exists between pesticides and Parkinson's disease (PD). To date, paraquat, maneb, and ziram — common chemicals sprayed in California's Central Valley and elsewhere — have been tied to increases in the disease, not only among farm workers but also in individuals who lived or worked near fields and likely inhaled drifting particles.

Now, UCLA researchers have discovered a link between PD and another pesticide, benomyl, whose toxicological effects still linger some 10 years after the chemical was banned by the U.S. Environmental Protection Agency.

Moreover, the new research suggests that the damaging series of events set in motion by benomyl may also occur in people with PD who were never exposed to the pesticide, according to senior author Dr. Jeff Bronstein. Exposure to benomyl, he says, starts a cascade of cellular events that may lead to PD. The pesticide prevents an enzyme, aldehyde dehydrogenase (ALDH), from suppressing DOPAL, a toxin that naturally occurs in the brain. When left unchecked by ALDH, DOPAL accumulates, damages neurons, and increases an individual's risk of developing PD.

The investigators believe their findings regarding benomyl may be generalized to all PD patients. Developing new drugs to protect ALDH activity, they say, may eventually help slow the progression of the disease, whether or not an individual has been exposed to pesticides.

The new research appears in the current online edition of the Proceedings of the National Academy of Sciences.

PD is a debilitating neurodegenerative disorder that affects millions of people worldwide. Its symptoms — including tremor, rigidity, and slowed movements and speech — increase with the progressive degeneration of neurons, primarily in a part of the mid-brain called the substantia nigra. This area normally produces dopamine, a neurotransmitter that allows cells to communicate, and damage to the mid-brain has been linked to the disease. Usually, by the time the symptoms of PD have become apparent, more than half of these neurons, known as dopaminergic neurons, have been lost.

Until now, evidence had pointed to one particular culprit — a protein called alpha-synuclein — in the development of PD. This protein, common to all PD patients, is thought to create a pathway to the disease when it binds together in “clumps” and becomes toxic, killing the brain’s neurons.

The identification of ALDH activity now gives researchers another target to focus on in trying to stop the disease.

“We’ve known that in animal models and cell cultures, agricultural pesticides trigger a neurodegenerative process that leads to Parkinson’s,” said Bronstein. “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.”

Source: UCLA; January 3, 2013.

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