Neuro-Immune Interactions in Parkinson's Disease

Parkinson's disease is a prevalent neurodegenerative disorder wherein recent evidence suggests pathogenesis may be medicated by inflammatory processes. The molecular architecture of the disease remains to be fully elucidated. We hypothesize that Parkinson's disease is initiated by an autoimmune process involving alpha-synuclein-specific T cell activation by gut microbiome dysbiosis, followed by neuro-immune interactions that establish the disease in the brain. We integrate neuroimmunology, single-cell genomics, mouse models, and microbiome approaches to examine whether T cell-mediated autoimmunity initiates the neurodegneration process in Parkinson's disease, and if these early immunological processes converge on classic archetypes of neurodegeneration. This work will produce an unprecedented map (the "interactome") of the neuro-immune interactions that are perturbed in Parkinson's disease, identifying rational targets for clinical trials and paving the way for the development of new treatments.