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• Posted April 25, 2024

Genes Could Mix With Pesticide Exposure to Raise Parkinson's Risk

It's long been known that exposure to agricultural pesticides can greatly raise a person's odds for Parkinson's disease.

New genetics research now reveals those who might be most vulnerable.

A team at the University of California, Los Angeles (UCLA), pored over genetic data from 800 Parkinson's patients living and working in that state's agricultural heartland, the Central Valley.

Many of these people "had long-term exposure to 10 pesticides used on cotton crops for at least a decade prior to developing the disease, with some patients having been exposed as far back as 1974," the researchers noted in a UCLA news release.

They honed in on certain gene variants connected to lysosomes, parts of cells that break down cellular waste. Impairment in lysosomal function has long been linked to the genesis of Parkinson's, explained a team led by Dr. Brent Fogel, a professor of neurology and human genetics at UCLA.

The variants associated with lysosomal processes were "enriched" in patients who'd had prolonged exposures to pesticides, the study showed.

The findings were published April 25 in the journal NPJ Parkinson's Disease.

These gene variants also appeared to interfere with proper protein function. According to the researchers, this suggests that aberrant waste-disposal in the cell could be an underlying cause of Parkinson's, occurring alongside chronic exposure to pesticides.

As toxic compounds -- including a protein called alpha synuclein, long linked to Parkinson's -- build up in brain cells, they can form what are known as Lewy bodies in tissues. Lewy body accumulation is a hallmark of Parkinson's in the brain, the researchers noted.

"The study supports the hypothesis that the genetic predisposition comes from minor changes in genes that are associated with lysosomal function,"Fogel said in a UCLA news release.

"On a day-to-day basis, these variants are not having much of an impact," he added. "But under the right stress, such as exposure to certain pesticides, they can fail and that could, over time, lead to the development of Parkinson's disease. This is called a gene-environment interaction." 

Could there be other gene variants predisposing people to risk, acting on other neurological pathways? It's very possible, said study co-lead author Dr. Kimberly Paul.

"These patients were susceptible somehow and if we can figure out why they were susceptible, maybe we can act on those pathways,"said Paul, an assistant professor of neurology at UCLA.

"There are data for a lot of common disorders suggesting that environmental influences impact the development of these diseases, but we don't yet have a good way of measuring that impact or determining who is specifically at risk,"Fogel said. "This is a step forward in that direction." 

More information

There's much more on Parkinson's disease at the Parkinson's Foundation.

SOURCE: University of California, Los Angeles, news release, April 25, 2024