Parkinson’s disease is often categorized as a physical disease due to its degenerative impact on movement, balance, and coordination. However, Parkinson’s disease can also lead to cognitive symptoms. Over time, the cognitive changes can progress to a condition formally known as Parkinson’s disease dementia, or PDD. Despite innovations in treatment for the motor symptoms associated with the disease, at this time, there are no effective treatments for PDD. However, a recent study published in the journal Experimental Neurology may have identified a protein with the potential to protect brain cells. If the protein can produce a favorable clinical response, it could be used to treat Parkinson’s disease and related disorders. Read on to delve into this intriguing study of the PNA5 protein, which involved the Line 61 mouse model of Parkinson’s disease.
Evaluating PNA5 Using the Line 61 Mouse Model
The research team was led by Lalitha Madhavan, MD, Ph.D., an associate professor of neurology at the University of Arizona College of Medicine, Tucson. Madhavan’s team sought to investigate the PNA5 protein, a novel Mas receptor agonist, using a mouse model of Parkinson’s disease. To explore the impact of the PNA5 protein, the team used the Line 61 mouse model of Parkinson’s disease — mice engineered to over-express human wild type α-synuclein (α-syn) under the Thy1 promoter (Thy1 α-syn mice, “Line 61”). This mouse was selected as a model of Parkinson’s disease as it presents cognitive decline.
PNA5 Protein Targets Inflammation
Neurodegenerative diseases like Parkinson’s disease and Alzheimer’s disease are frequently linked to chronic inflammation. In the case of Parkinson’s disease, microglia — a type of immune cell in the brain — are known to enter an overactivated state. “Normally, microglia are looking for things like viruses or injury and secreting substances that block off the damage,” noted Kelsey Bernard, Ph.D., the study’s first author. “In Parkinson’s disease, when they’re constantly activated, microglia can propagate further damage to the surrounding tissue. That’s what we see in Parkinson’s brains, particularly in regions associated with cognitive decline.”
The team found that, in the mouse model, these overactive microglia “flooded” their environments with an inflammatory chemical. “This inflammatory chemical can directly interact with neurons in a region of the brain important for learning and memory,” Bernard said. However, after the mouse model was treated with PNA5, the team saw a reduction in blood levels of the inflammatory chemical created by the microglia. This correlated directly with a reduced loss in brain cells, suggesting that PNA5 could slow cognitive decline associated with inflammation. Moving forward, the researchers hope to refine the suppression of this inflammatory chemical, with the goal of protecting the brain and slowing cognitive decline.
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Madhavan, who led the research team, hopes the team’s research into PNA5 will eventually lead to a druggable solution for individuals with PDD. “PNA5 seems to have a possibility of stopping or delaying Parkinson’s progression to some extent,” she said, “and could improve the health of brain cells or prevent cells from dying.”
To study Parkinson’s disease, Scantox Neuro offers the Line 61 mouse model that was used in the study presented above. We also offer the hA53Ttg mouse model, which expresses human α-synuclein with A53T mutation, for in vivo Parkinson’s disease research. Animals can be evaluated for disease-specific modifications by different behavioral tests, evaluating motor deficits or cognitive alterations. Scantox Neuro further offers several in vitro approaches to evaluate lesion-induced neurotoxicity, mitochondrial impairment, as well as α-synuclein aggregation, seeding, and autophagy. The pathology of all in vivo and in vitro models can be evaluated by several histological and biochemical methods.
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