Researchers at the University of Arizona Health Sciences have identified a small protein known as PNA5 that may protect brain cells and offer new treatment avenues for the cognitive symptoms associated with Parkinson’s disease. This groundbreaking study highlights the potential for PNA5 to address cognitive decline and related disorders that frequently accompany this neurological condition.
Parkinson’s disease is primarily recognized for its motor symptoms, including tremors, stiffness, and slow movement. However, cognitive issues, which can escalate to Parkinson’s dementia, are also significant. Current treatments effectively manage motor symptoms, but there are no approved therapies for cognitive impairment.
According to Dr. Lalitha Madhavan, an associate professor of neurology at the University of Arizona College of Medicine – Tucson, “When patients are diagnosed with Parkinson’s disease, 25% to 30% already exhibit mild cognitive impairment. As the disease progresses, 50% to 70% of patients report cognitive challenges. Unfortunately, we lack effective treatments for cognitive decline or dementia in Parkinson’s disease.”
The research team, led by Madhavan and including Dr. Torsten Falk, a research professor of neurology, investigated PNA5, a protein developed by Dr. Meredith Hay, a professor of physiology. Their findings, published in Experimental Neurology, indicate that PNA5 may have a protective effect on brain cells in an animal model.
“With PNA5, we’re specifically targeting cognitive symptoms and aiming to prevent further degeneration,” said Kelsey Bernard, PhD, a postdoctoral researcher and the study’s first author. “By focusing on protection, we hope to halt cognitive decline.”
The precise causes of neurodegenerative diseases like Parkinson’s remain largely unknown, but inflammation is believed to play a critical role. While inflammation is a normal immune response to injury or infection, chronic inflammation can lead to significant damage.
Bernard explained that in Parkinson’s disease, microglia—immune cells in the brain—can become overactive, contributing to further damage. “Normally, microglia seek out viruses or injuries and release substances to mitigate damage,” she noted. “However, when they are constantly activated, they can exacerbate damage to surrounding tissues, particularly in areas of the brain linked to cognitive function.”
The research team discovered that these hyperactive microglia release an inflammatory chemical associated with cognitive decline. After administering PNA5, they observed a decrease in blood levels of this inflammatory substance, correlating with a reduction in brain cell loss. They believe PNA5 helps normalize the microglia’s immune response, potentially offering protective benefits to the brain.
PNA5 was developed by modifying a naturally occurring chemical in the body, enhancing its ability to penetrate the brain and remain effective longer. Hay is also exploring PNA5’s potential in treating other forms of dementia, including vascular dementia and Alzheimer’s disease.
Dr. Madhavan expressed optimism about the research, stating, “It has already been tested in other models, which makes me hopeful.” She envisions a future where PNA5 could serve as a treatment option for cognitive symptoms in Parkinson’s patients, who may still require other medications for motor symptoms.
“I see it as one part of a larger solution,” Madhavan noted. “Managing Parkinson’s is complex, and multiple medications may be necessary. The interconnectedness of brain functions adds to this complexity.”
The research team plans to conduct further studies to identify biomarkers, refine dosing, investigate sex differences, and explore the mechanisms by which PNA5 operates.
“PNA5 shows potential for slowing or delaying the progression of Parkinson’s and may improve brain cell health,” Madhavan added.
This study is part of Bernard’s doctoral research, conducted under the guidance of co-senior authors Madhavan and Falk. “The brain is the most intriguing part of the body,” Bernard remarked. “Understanding what causes brain cells to function correctly—and what leads them astray—is a captivating challenge.”
The research received support from the Michael J. Fox Foundation, the National Institutes of Health, and the ARCS Foundation Scholarship.
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