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Tuesday, March 26, 2024

UCLA researchers link common pesticides to Parkinson’s disease

A team of medical researchers at UCLA has drawn an unnerving link between pesticide exposure and an increased risk for Parkinson’s disease. For individuals of a genetically at-risk population, even low levels of exposure can exponentially increase the likelihood of developing the disease. The research was published in the Feb. 4 issue of the journal Neurology.

Parkinson’s disease is the progressive degradation of an individual’s capacity to move in a smooth, stable fashion. This chronic disorder involves the loss of function and eventual death of indispensable neuronal tissue in the brain, specifically of the substantia nigra region (this is the region responsible for voluntary movement). One of the primary functions of the endangered neuron population is the synthesis of dopamine, a neurotransmitter that is key for movement control and coordination. As Parkinson’s disease progresses, the declining neural population of the substantia nigra region is unable to secrete adequate levels of dopamine for an individual to produce coordinated movement. What begins as a faint quiver eventually progresses into a pronounced loss of muscular control.

“Impaired balance and gait tends to affect patients’ activities of daily living and the tremors can further impede patients’ fine motor function such as writing, eating and working,” said Lin Zhang, director of the Movement Disorders Program of the Sacramento Veterans Affairs Medical Center.

Initially, the UCLA team discovered a link between Parkinson’s and the pesticide benomyl, which has been banned from use by the U.S. Environmental Protection Agency. While benomyl’s selective toxicity was intended to target microorganisms, invertebrates and earthworms, the research team revealed that benomyl and an assortment of common, currently used agricultural and industrial pesticides may have similarly devastating consequences. Used in the production of organic/inorganic foods, maintenance of golf courses and the sterilization of commercial buildings and homes, these chemicals may trigger the chronic effects of Parkinson’s through the inhibition of a crucial toxin-degrading enzyme, aldehyde dehydrogenase (ALDH) — coincidentally one of the primary enzymes involved in alcohol metabolism.

According to study author Jeff Bronstein, people with a relatively common variation to the genetic sequence that codes for ALDH are particularly sensitive to the effects of ALDH-inhibiting pesticides. ALDH inhibition prevents the degradation of toxic aldehydes into less toxic byproducts that can more easily be dealt with by the body. In individuals with insufficient ALDH enzyme, the toxic aldehydes build up and cause harm to dopamine-producing cells. As dopamine concentrations decrease over time, an individual’s risk for developing Parkinson’s increases.

The study was conducted on a group of 360 patients with Parkinson’s disease from three different agriculture-heavy counties in Central California. Additionally, 816 people from the same area who did not have Parkinson’s were recruited for the study. The team of researchers focused their analyses on individuals with ambient exposures to pesticides at work and at home, and used information from the California Department of Pesticide Regulation to determine approximate levels of exposure.

“In this study we looked at a certain region of the polymorphic gene in question; we found seven different genetic variants, but you can cluster them into two major categories: The first class is ‘clade 1’ and composes roughly 65 percent of individuals; approximately 35 percent are ‘clade 2.’ In the absence of pesticide exposure the variation alone doesn’t increase an individual’s risk of developing Parkinson’s much, but for the individuals of clade 2, exposure to the pesticides does increase the risk [several-fold],” Bronstein said.

The key takeaway point from Dr. Bronstein’s statement is that in a perfect environment, individuals in either clade 1 or clade 2 would not see an increased risk for Parkinson’s; expose this population to certain pesticides, however, and everyone, especially clade 2 members, becomes susceptible. It’s not that clade 2 members have a higher overall risk of developing Parkinson’s, it’s simply that this population is more significantly impacted by pesticides when they are present.

“For the vulnerable populations, inhalation and ingestion of the chemicals were the primary routes of exposure,” said Beate Ritz, UCLA professor of epidemiology.

It is important for potentially exposed individuals to wear gloves, masks and protective equipment when pesticides are being applied, and to know what pesticides are being used. A primary focus of this study and the work surrounding it is to identify the mechanisms by which the environment may contribute to Parkinson’s disease. The ultimate goal is to develop ways to treat it.

Pesticides are a perfect reminder of the potential dangers that human ingenuity poses to many species, including our own. These chemicals, which are designed with the sole purpose of benefiting humanity, may be our downfall if we aren’t thorough in testing their biochemical consequences.

 

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