LOS ANGELES, June 16 (UPI) -- Researchers found a widely used pesticide can cause Parkinson's disease by increasing concentrations of a protein in the brain, suggesting targeting the protein may help patients whose condition is not related to pesticide exposure.
The fungicide ziram is linked to Parkinson's cases not explained by genetics, but a new understanding of its effect on increasing levels of the protein α-synuclein could help treat the disease in all patients, researchers at the University of California Los Angeles report.
Ziram is part of a group of pesticides called dithiocarbamates that have long been linked to Parkinson's disease, a progressive disorder of the nervous system caused by the death of dopamine-producing neurons in the brain.
Clumps of the α-synuclein protein form in the brains of Parkinson's patients, disrupting the neurons and contributing to the movement problems typical of patients with the disease. In experiments with zebrafish, the researchers found preventing the increased appearance of α-synuclein in their brains prevented swimming issues after they'd been exposed to ziram.
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The researchers think the finding could be significant as more than 70 percent of Parkinson's disease cases are not caused by genetic mutation.
"This is important -- it establishes that environmental toxins work on same pathway that is in play in those genetically disposed to Parkinson's," Dr. Jeff Bronstein, a professor of neurology and director of movement disorder research at the University of California Los Angeles, said in a press release. "Most important, we can use drugs being developed now on patients who get Parkinson's because of ziram exposure."
For the study, published in the journal Environmental Health Perspectives, researchers developed a Parkinson's model in zebrafish, exposing them to ziram to cause the loss of dopamine common to Parkinson's patients. The fish did not swim properly, which the researchers considered evidence of the condition.
After genetically knocking out the α-synuclein protein and exposing the fish to ziram, they continued to swim properly -- suggesting the lack of the protein protected them.
To test the theory further, the researchers treated fish with the protein using a drug called CLR01 that breaks up protein clumps like those found in Parkinson's patients, finding the fish continued to swim properly.
The researchers say future research is needed to learn whether other pesticides or substances have the same Parkinson's-causing effects, and further testing CLR01 on the way to testing the drug in human clinical trials.
"These findings add to the growing literature linking pesticide exposure and the development of Parkinson's disease and offers important insights into the mechanisms of ziram toxicity," Bronstein said. "A better understanding of the pathogenesis of Parkinson's disease will ultimately lead to new treatments and eventually a cure."
