Mechanism of Anti-alpha-Synuclein Immunotherapy

Immunization therapy targeting alpha-synuclein has emerged as a promising approach for Parkinson's disease and perhaps for other synucleinopathies. Several antibodies have shown therapeutic effects in mouse models of synucleinopathies and have alleviated the pathological and behavioral phenotypes of these mice. The mechanisms through which the immunization therapy works were initially puzzling, especially given that alpha-synuclein is a typical cytosolic protein. Recent studies, however, suggested that extracellular alpha-synuclein is an important pathogenic entity, and hence, a target for immunotherapy. Here, we review the literature describing immunization therapy for synucleinopathies in mouse models and provide current thoughts on the potential mechanisms underlying the therapeutic effects of alpha-synuclein immunotherapy.