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In Parkinson Disease, Inflammation May Play Causative Role
A growing body of evidence suggests inflammation could play a causative role in Parkinson disease, according to a special supplement to the Journal of Parkinson’s Disease that covers recent research breakthroughs on the links between immune activation, neuroinflammation, and Parkinson disease.
“Parkinson disease risk is influenced by many factors including a mix of immunogenetics and the environment, such as infection history,” commented guest editors Bastiaan R. Bloem, MD, PhD, Patrik Brundin, MD, PhD, Ashley Harms, PhD, Cecilia Lindestam Arlehamn, PhD, Eng King Tan, MD, and Caroline Williams-Gray, PhD. “In recent years, increasing evidence suggests an association with autoimmune conditions and involvement of the immune system or its aberrant responses in patients with Parkinson disease and various experimental models.”
A review article in the supplement explains how peripheral T lymphocytes can enter into brain areas primarily affected in Parkinson disease. According to coauthors Benjamin D. Hobson, MD/PhD student, and David Sulzer, PhD, both of Columbia University Irving Medical Center, New York, neurons can present antigens bound to MHC class 1 molecules on the cell surface and signal the cell’s physiological state to immune cells, such as T cells. Certain subtypes of T cells (CD8+) have been shown to bind to the antigen: MHC class 1 complex on the cell surface, promoting immune responses that cause cell damage and ultimately neuronal death.
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“Recent animal models suggest the possibility of T cell autoreactivity to mitochondrial antigens in Parkinson disease,” said Dr Sulzer. “However, it remains unclear if neuronal antigen presentation plays a role in Parkinson disease or other neurodegenerative disorders, and efforts are underway to better understand the potential impact of autoimmune responses on neurodegeneration.”
“In summary,” the team of guest editors noted, “multiple independent studies in clinical and preclinical models have provided corroborative evidence of the involvement of central and peripheral immune and inflammatory processes in Parkinson disease. Our knowledge of how the immune system contributes to Parkinson disease pathogenesis is constantly evolving, with increasing evidence for a role of several genes and susceptibility loci.”
Substantial research is still needed to understand the individual and collective roles of immune cells and their subsets, the editors pointed out, as well as how they interact with each other and with alpha-synuclein and other key proteins.
References
Growing evidence for the role of the immune system in Parkinson’s disease. News release.
