Exercise Effects on Synuclein Aggregation, Neuroinflammation, and Neurodegeneration
Abstract
Parkinsons disease is the second most common neurodegenerative disorder. An estimated 1,000,000 United States residents will be living with Parkinsons disease by 2020, which will create a profound health and economic burden. There exist treatments for the symptoms of the disease but as the disease progresses these treatments are no longer effective. Therefore, it is of critical importance that therapies that slow or halt the progression of PD are identified. Preclinical and clinical studies suggest that exercise therapy may slow the progression of Parkinsons disease; however, overall results are inconclusive. Our ability to properly evaluate the disease-modifying potential of exercise has been hindered by two main issues: First, in clinical studies it is difficult to determine whether any improvements observed are due to symptomatic improvement versus the sparing of neurons or slowing pathology in the brain since we have limited ability to quantify neurons and Parkinsons pathology in the living human brain. Second, our ability to turn to preclinical animal models has been limited by the model tools we have had, models that do not accurately reproduce the key pathological feature of the Parkinsonian brain, alpha-synuclein accumulation. The present application seeks to use an optimized preclinical model of Parkinsons disease to examine whether exercise therapy can protect against this hallmark pathology of Parkinsons disease and the subsequent loss of neurons. We will also examine the mechanism whereby the effects of exercise may occur and the effect on behavior affected in Parkinsons disease including motor, cognitive, and neuropsychiatric function. This proposed research addresses the FY18 PRP IIRA Focus Area Biological mechanisms of impact from exercise on neurodegeneration in Parkinsons disease directly by examining the effect of exercise in this optimized preclinical Parkinsons disease model and mechanisms related to accumulation of the toxic protein alpha-synuclein, neuroinflammation, and expression of substances in the brain called trophic factors. Results from this research could help individuals afflicted by Parkinsons disease. If exercise is truly disease-modifying then it would provide a much needed, non-invasive, non-pharmacological, low-cost therapeutic strategy for Parkinsons disease patients and at-risk populations, including military Veterans. Exercise therapy could be made readily available through hospitals and VA systems across the country.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910771
Entities
People
- Caryl Sortwell
Organizations
- Michigan State University
- United States Army