A functional role for alpha-synuclein in neuroimmune responses

Alpha-synuclein is a neuronal protein with unclear function but is associated with the pathogenesis of Parkinson's disease and other synucleinopathies. In this review, we discuss the emerging functional role of alpha-synuclein in support of the unique immune responses in the nervous system. Recent data now show that alpha-synuclein functions to support interferon signaling within neurons and is released from neurons to support chemoattraction and activation of local glial cells and infiltrating immune cells. Inflammatory activation and interferon signaling also induce post-translational modifications of alpha-synuclein that are commonly associated with Parkinson's disease pathogenesis. Taken together, emerging data implicate complex interactions between alpha-synuclein and host immune responses that may contribute to the pathogenesis of Parkinson's disease. Additional study of the function of alpha-synuclein in the brain's immune response may provide disease-modifying therapeutic targets for Parkinson's disease in the future. •Alpha-synuclein is associated with the pathogenesis of Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy.•Recent work has shown that alpha-synuclein functions to support neuronal and microglia innate immune responses.•Alpha-synuclein interacts with the type 1 interferon signaling pathway in neurons to support interferon stimulated gene expression.•Alpha-synuclein is released from neurons resulting in activation of microglia, astrocytes, and infiltrating innate and adaptive immune cells.