A recent study conducted by researchers from the University of Arizona Health Sciences has discovered that a small protein known as PNA5 might help protect brain cells, opening the door for potential treatments targeting cognitive symptoms in Parkinson’s disease and related conditions.
A recent study conducted by researchers from the University of Arizona Health Sciences has discovered that a small protein known as PNA5 might help protect brain cells, which could lead to treatments for the cognitive symptoms of Parkinson’s disease and related conditions.
Parkinson’s disease is a neurological condition that is commonly recognized for its tremors, muscle stiffness, sluggish movements, and balance issues. However, it also causes cognitive difficulties that can progress to Parkinson’s dementia. While there are treatments available to manage the motor symptoms, effective therapies for cognitive issues remain elusive.
“When patients receive a diagnosis of Parkinson’s disease, about 25% to 30% already exhibit mild cognitive impairment. As the disease advances, 50% to 70% of patients report experiencing cognitive problems,” explained Dr. Lalitha Madhavan, an associate professor of neurology at the University of Arizona College of Medicine – Tucson. “Unfortunately, we lack effective methods for addressing cognitive decline or dementia in Parkinson’s disease.”
Dr. Madhavan leads a research team in collaboration with Dr. Torsten Falk, a research professor of neurology, to explore PNA5, a protein developed by Dr. Meredith Hay, a professor of physiology. They recently published findings in Experimental Neurology indicating that, in animal studies, PNA5 may have protective effects on brain cells.
“Our objective with PNA5 is to tackle cognitive symptoms, particularly aiming to halt further degeneration,” stated Dr. Kelsey Bernard, a postdoctoral researcher in the Madhavan Lab and the lead author of the study. “By focusing on protection, we hope to prevent ongoing cognitive decline.”
Reducing Inflammation
The exact origins of neurodegenerative diseases largely remain unclear, but current theories suggest inflammation—a normal immune response to infections or injuries—could be a key factor. If inflammation becomes chronic, it can lead to significant damage.
According to Bernard, inflammation plays a crucial role in Parkinson’s disease when microglia, the brain’s immune cells, enter an overactive state.
“Typically, microglia are involved in detecting viruses or injuries and sending out chemicals to mitigate damage,” she noted. “However, in Parkinson’s disease, when these cells remain persistently active, they can contribute to additional harm in surrounding tissues. This detrimental effect is particularly evident in Parkinson’s brains, especially in areas related to cognitive decline.”
The study revealed that these hyperactive microglia release high levels of an inflammatory compound, confirming previous research linking this compound to cognitive health.
“This inflammatory substance interacts directly with neurons in brain regions vital for learning and memory,” Bernard remarked.
Post-treatment with PNA5, the researchers observed a reduction in levels of the inflammatory compound in the blood, which corresponded with less loss of brain cells. They believe that PNA5 helps revert the microglia’s overly aggressive immune activity back to a more typical state.
The research team aspires to lessen the production of the inflammatory compound through PNA5 to safeguard the brain.
Widening Treatment Avenues
In developing PNA5, Dr. Hay, in partnership with Dr. Robin Polt, a professor of chemistry and biochemistry at the University’s College of Science, made slight modifications to a naturally occurring chemical in the body to enhance its ability to penetrate the brain and prolong its presence there. Dr. Hay is also exploring PNA5’s potential to address other forms of dementia, including vascular dementia and Alzheimer’s disease.
“It has been successfully tested in various models, which makes me feel more hopeful,” Dr. Madhavan stated. Along with Polt and Hay, Madhavan is a member of the BIO5 Institute.
She anticipates that the research on PNA5 could eventually yield a medication that Parkinson’s patients can take to manage cognitive symptoms, even though additional medications might be necessary for motor symptom control.
“I view it as one piece of a larger puzzle—there will be other medications addressing different aspects of Parkinson’s. While taking multiple medications is not ideal, it’s a complex condition that requires multifaceted solutions,” she said. “The interconnectedness of brain functions is remarkable, yet it adds to the overall complexity.”
The team intends to conduct further studies aimed at identifying biomarkers, fine-tuning dosages, exploring sex-based differences, and understanding how PNA5 functions.
“PNA5 appears to hold promise in halting or delaying the progression of Parkinson’s disease and may enhance the health of brain cells or prevent cell death,” Madhavan stated.
This publication is based on Bernard’s doctoral research conducted under the mentorship of co-senior authors Madhavan and Falk.
“The brain is the most intriguing part of the body,” Bernard noted. “These cells are fascinating – understanding what makes them function properly and what causes them to malfunction is crucial.”
This research was partially funded by the Michael J. Fox Foundation (award no. MJFF 024922), the National Institutes of Health (award no. T32 AG1081797), and the ARCS Foundation Scholarship.
