Affiliations: Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Alabama, USA | Department of Neurobiology, University of Alabama at Birmingham, Alabama, USA
Note: [] Correspondence to: David G. Standaert, Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, 516 Civitan International Research Center, 1719 6th Avenue South, Birmingham, Alabama 35294-0017, USA. Tel.: +1 205 996 6329; Fax: +1 205 996 6580; E-mail: [email protected]
Abstract: Alpha-synuclein (α-syn) is central to the pathogenesis of Parkinson disease (PD). Gene duplications, triplications and point mutations in SNCA1, the gene encoding α-syn, cause autosomal dominant forms of PD. Aggregated and post-translationally modified forms of α-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 α-syn to produce spreading pathology. Accumulation of abnormal forms of α-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 α-syn and subsequent inflammation may reveal novel targets for neuroprotective interventions. In this review, we examine the role of α-syn and modified forms of this protein in the initiation of innate and adaptive immune responses.
