Role of α-Synuclein in Inducing Innate and Adaptive Immunity in Parkinson Disease

Alpha-synuclein (alpha-syn) is central to the pathogenesis of Parkinson disease (PD). Gene duplications, triplications and point mutations in SNCA1, the gene encoding alpha-syn, cause autosomal dominant forms of PD. Aggregated and post-translationally modified forms of alpha-syn are present in Lewy bodies and Lewy neurites in both sporadic and familial PD, and recent work has emphasized the prion-like ability of aggregated alpha-syn to produce spreading pathology. Accumulation of abnormal forms of alpha-syn is a trigger for PD, but recent evidence suggests that much of the downstream neurodegeneration may result from inflammatory responses. Components of both the innate and adaptive immune systems are activated in PD, and influencing interactions between innate and adaptive immune components has been shown to modify the pathological process in animal models of PD. Understanding the relationship between alpha-syn and subsequent inflammation may reveal novel targets for neuroprotective interventions. In this review, we examine the role of alpha-syn and modified forms of this protein in the initiation of innate and adaptive immune responses.