Epigenetic changes linked to 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 died with 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 affected genes were almost completely different in men and women.
You could illustrate the male-female divide 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’ve found this every time we’ve looked at males and females separately, regardless of whether we’ve been looking 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, lead author, assistant professor of pharmacology and toxicology at the Ernest Mario School of Pharmacy
Parkinson’s causes the death of key neurons in a region of the brain that produces the neurotransmitter dopamine. Epigenetic changes — changes in how genes work, but not the underlying genetic code — that contribute to the disease are not fully understood, but the study’s results give researchers hundreds of more candidates to explore
“Some of the genes we found had already been implicated in other studies, but many of them were new, so this study opens up many avenues for further research into how these other genes are connected to Parkinson’s,” Bernstein said.
Parkinson’s, a brain disorder that affects men at a higher rate than women in the United States, is the second most common neurodegenerative disease behind Alzheimer’s, the CDC shows. Although up to 10 percent of cases are entirely genetic, the rest appear to result from a complex interplay of genes, age, and environmental factors.
To learn more about the epigenetic marks associated with Parkinson’s, the researchers took anonymous samples of brain tissue from the parietal cortices of 50 people who died with mid-stage Parkinson’s disease and 50 with healthy brains. They separated male and female brains and then separated the neurons from other cell types to investigate how epigenetic changes in these particular cells preceded neuron death in Parkinson’s disease patients.
“The study does not allow us to say that epigenetic changes in these genes cause Parkinson’s. It may be that Parkinson’s causes changes in these genes,” Bernstein said. “We are doing more studies in the lab to determine if these changes contribute to the disease.”
Ideally, Bernstein added, this work will help identify genes and 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 trauma to the brain and chronic exposure to certain chemicals increase the risk of developing the disease, while caffeine and nicotine consumption lower it somewhat. Although L-DOPA and several other medications relieve symptoms, and several trials of new drugs are underway, no currently approved medication slows the progression of the disease.
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Journal reference:
Kochmanski, J., et al. (2022) Parkinson’s disease-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.