June 13, 2024
Parkinson's Disease

Genetic Susceptibility to Parkinson’s Disease: A New Study Reveals the Role of Lysosomal Genes in Long-Term Pesticide Exposure

A groundbreaking study published in the journal npj Parkinson’s Disease by UCLA Health researchers has identified specific genetic variants that may explain why some individuals with long-term pesticide exposure develop Parkinson’s disease, while others do not.

Decades of research have linked pesticide exposure to an increased risk of Parkinson’s disease. However, the reason why some individuals with high exposure develop the disease, while others do not, has remained a mystery. One hypothesis suggests that susceptibility to the disease is a combination of both environmental and genetic factors.

The new study, which involved genetic data from nearly 800 Central Valley (California) residents with Parkinson’s disease, many of whom had been exposed to 10 pesticides used on cotton crops for at least a decade prior to developing the disease, sheds light on this question.

The researchers examined the study participants’ genetic makeup for rare variants in genes associated with the function of lysosomes—cellular compartments that break down waste and debris in cells, thought to be involved in the development of Parkinson’s disease—and looked for an enrichment of these variants in patients with high pesticide exposure compared to a representative sample of the general population.

The researchers found that variants in these genes were more common in patients with more severe Parkinson’s disease and higher pesticide exposure. These genetic variants also appeared to be deleterious to protein function, suggesting that disruption of lysosomal activity may be underlying the development of Parkinson’s disease combined with pesticide exposure.

Dr. Brent Fogel, the study’s corresponding author and professor of Neurology and Human Genetics at UCLA, explained that while the specific interactions between pesticides and the expression of these genetic variants require further study, the results suggest that in someone with these variants, long-term exposure to cotton pesticides could lead to the buildup of toxic compounds due to alterations of the cells’ ability to break down damaged proteins and organelles, a process known as autophagy, and thus contribute to the development of Parkinson’s disease.

Previous studies have shown that altered autophagy can result in the buildup of a protein called alpha-synuclein, which is abundant in the brain and neurons. As the protein builds up, it forms clumps known as Lewy bodies, which are a pathological hallmark of Parkinson’s disease.

Dr. Kimberly Paul, the study’s co-lead author and assistant professor of Neurology at UCLA, noted that Parkinson’s disease is the fastest growing neurodegenerative disease in the world. While an increase in the number of new patients is expected due to the large aging population in the U.S., the rate of new Parkinson’s disease patients is outpacing the rate that is expected from aging alone.

Paul added that the findings of the new study raise the question of whether there are other genetic variants that may be altering the susceptibility to Parkinson’s disease among this population, including other biological pathways affected by different types of pesticides.

“These patients were susceptible somehow, and if we can figure out why they were susceptible, maybe we can act on those pathways,” Paul said.

Fogel noted that the findings build on decades of research by UCLA Health investigators Drs. Jeff Bronstein and Beate Ritz into the associations between pesticide exposure and Parkinson’s disease risk in the Central Valley.

The study represents a step forward in understanding the role of genetic susceptibility in the development of Parkinson’s disease in the context of environmental exposures. Further research is needed to determine the specific interactions between pesticides and the expression of these genetic variants and to identify potential interventions to mitigate the risk of Parkinson’s disease in susceptible individuals.

Note:
1. Source: Coherent Market Insights, Public sources, Desk research.
2. We have leveraged AI tools to mine information and compile it.