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Epigenetic changes associated with Parkinson's disease are different in men and women, study shows
The epigenetic changes associated with Parkinson's disease — a nervous system disorder that affects nearly 1 million Americans — are different in men and women, according to a new Rutgers study published in NPJ Parkinson's Disease. In a postmortem analysis of brain neurons, researchers compared samples from 50 people who had died of Parkinson's and 50 who had no signs of the disease. They found more than 200 genes with different epigenetic marks in diseased and healthy brains - but the genes affected were almost completely different in men and women. They could narrow the gap between men and women...
Epigenetic changes associated with Parkinson's disease are different in men and women, study shows
The epigenetic changes associated with Parkinson's disease — a nervous system disorder that affects nearly 1 million Americans — are different in men and women, according to a new Rutgers study published in NPJ Parkinson's Disease.
In a postmortem analysis of brain neurons, researchers compared samples from 50 people who had died of Parkinson's and 50 who had no signs of the disease. They found more than 200 genes with different epigenetic marks in diseased and healthy brains - but the genes affected were almost completely different in men and women.
You could illustrate the gap between men and women with two circles representing genes with different epigenetic marks in Parkinson's disease, one for men and one for women, and the overlap between the circles would contain only five genes. And we found this every time we looked at males and females separately, whether we looked at humans or mice or toxicology models. What we call Parkinson’s disease in the singular is probably Parkinson’s disease in the plural.”
Alison Bernstein, senior author, assistant professor of pharmacology and toxicology at the Ernest Mario School of Pharmacy
Parkinson's causes the death of important neurons in a region of the brain that produces the neurotransmitter dopamine. The epigenetic changes — that is, changes in how genes work but not in the underlying genetic code — that contribute to the disease are not fully understood, but the study results give researchers hundreds more candidates to explore.
"Some of the genes we found have already been implicated in other studies, but many of them were brand new, so this study opens up a lot of opportunities for further investigation into how these other genes are related to Parkinson's," Bernstein said.
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Parkinson's, a brain disease that affects men more often than women in the U.S., is the second most common neurodegenerative disease after Alzheimer's, CDC figures show. While up to 10 percent of cases are entirely genetic, the remainder appear to be due to a complex interplay of genes, age and environmental factors.
To learn more about epigenetic marks associated with Parkinson's disease, researchers took anonymized brain tissue samples from the parietal cortices of 50 people who died of mid-stage Parkinson's disease and 50 with healthy brains. They separated male brains from female brains and then neurons from other cell types to study how epigenetic changes in these particular cells change before neuron death in patients with Parkinson's disease.
"The study does not allow us to say that the epigenetic changes in these genes cause Parkinson's. It may be that Parkinson's causes changes in these genes," Bernstein said. “We are conducting further studies in the laboratory to determine whether these changes contribute to disease.”
Ideally, Bernstein added, this work will help identify genes and signaling pathways that change early in the disease. These genes would be potential targets for treatments that could prevent or slow disease progression.
As things stand, efforts to predict, prevent or reverse Parkinson's disease have made frustratingly slow progress.
Physical brain trauma and chronic exposure to some chemicals increase the risk of developing this disease, while consumption of caffeine and nicotine somewhat reduces it. While L-DOPA and several other drugs relieve symptoms and several trials of new drugs are underway, no currently approved drug slows disease progression.
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Reference:
Kochmanski, J., et al. (2022) Parkinson's-associated sex-specific changes in DNA methylation at PARK7 (DJ-1), SLC17A6 (VGLUT2), PTPRN2 (IA-2β), and NR4A2 (NURR1) in cortical neurons. npj Parkinson's disease. doi.org/10.1038/s41531-022-00355-2.
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