Researchers have identified ten chemicals harmful to Parkinson’s disease-related neurons.

New insights into the role of environmental toxins in Parkinson’s disease are provided by the discovery of ten pesticides that significantly damaged neurons implicated in the disease’s development by Harvard and UCLA Health researchers.

It has been difficult to identify which pesticides may increase Parkinson’s risk, despite the fact that environmental factors like pesticide exposure have been linked to the neurodegenerative disorder for a long time. Nearly 14,000 pesticide products with over 1,000 active ingredients are registered for use in California, the nation’s largest agricultural producer and exporter.

Ten pesticides that were directly toxic to dopaminergic neurons were identified by UCLA and Harvard researchers using a novel combination of epidemiology and toxicity screening that made use of the extensive pesticide use database in California. The neurons assume a critical role in deliberate development, and the passing of these neurons is a sign of Parkinson’s.

“We were able to implicate individual agents more strongly than any previous study, and it was done in an entirely agnostic manner. When you combine this type of agnostic screening with a field-to-bench paradigm, you can pinpoint pesticides that appear to be quite important in the disease.”

Kimberly Paul, Ph.D., a lead author and assistant professor of neurology at UCLA

In addition, the researchers discovered that co-exposure to pesticides commonly used in cotton farming combinations was more harmful than exposure to any one pesticide in that group.

In this study, which was published on May 16 in Nature Communications, UCLA researchers looked at the exposure history of 288 pesticides over decades among Parkinson’s disease patients from the Central Valley who had participated in previous studies.

The scientists had the option to decide long-term openness for every individual, and afterward, utilizing what they named an all-inclusive affiliation examination, they tried every pesticide independently for its relationship with Parkinson’s. The majority of the 53 pesticides found in this untargeted screening had not previously been investigated for a possible connection to Parkinson’s disease and are still in use.

Those results were shared for lab investigation by Richard Krolewski, MD, Ph.D., a teacher of nervous system science at Harvard and a nervous system specialist at Brigham and Women’s Medical Clinic. Induced pluripotent stem cells, a type of “blank slate” cell that can be reprogrammed into neurons that closely resemble those lost in Parkinson’s disease, were used to test the toxicity of the majority of these pesticides in dopaminergic neurons derived from Parkinson’s patients.
These neurons were found to be directly harmed by ten pesticides, including four insect poisons (dicofol, endosulfan, naled, and propargite), three herbicides (diquat, endothall, and trifluralin), and three fungicides (copper sulfate [basic and pentahydrate] and folpet). The majority of pesticides are still being used today in the US.

There is not much in common between these pesticides other than their toxicity to dopaminergic neurons. They are structurally distinct, have a variety of uses, and have not been previously classified as toxic.

According to California’s pesticide database, researchers also tested the toxicity of multiple pesticides that are frequently applied simultaneously to cotton fields. The most toxic combinations included trifluralin, one of California’s most widely used herbicides. Past exploration in the Horticultural Wellbeing Study, a huge examination project including pesticide implements, had likewise ensnared trifluralin in Parkinson’s.

Lead author and UCLA neurology assistant professor Kimberly Paul, Ph.D., stated that the study demonstrated that their method could broadly screen for pesticides linked to Parkinson’s disease and better comprehend the strength of these associations.

Paul stated, “We were able to implicate individual agents in a way that was completely agnostic, and it was done in a way that was more than any other study has ever done.” Pesticides that appear to be quite important to the disease can be identified when this type of agnostic screening and a field-to-bench paradigm are combined.

The specialists are next wanting to study epigenetic and metabolomic highlights connected with openness utilizing integrative omics to assist with depicting which biologic pathways are upset among Parkinson’s patients who experienced pesticide openness. At the Harvard/Brigham and Women’s labs, more in-depth mechanistic studies of the specific neuronal processes affected by pesticides like copper and trifluralin are also being conducted.

The lab work is centered around unmistakable impacts on dopamine neurons and cortical neurons, which are significant for the development and mental side effects of Parkinson’s patients separately. In order to better comprehend how pesticides affect the function of these crucial cells, basic science is also expanding to include studies of pesticides on non-neuronal cells in the brain known as the glia.

More information: Kimberly C. Paul et al, A pesticide and iPSC dopaminergic neuron screen identifies and classifies Parkinson-relevant pesticides, Nature Communications (2023). DOI: 10.1038/s41467-023-38215-z

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