Immunotherapy targeting neurodegenerative proteinopathies: α-synucleinopathies and tauopathies

Abstract

α-Synuclein and tau deposition in the central nervous system is responsible for various parkinsonian syndromes, including Par-kinson’s disease, multiple system atrophy, dementia with Lewy bodies, progressive supranuclear palsy and corticobasal degener-ation. Emerging evidence has suggested that pathologic α-synuclein and tau are transmitted from cell to cell and further acceler-ate the aggregation of pathologic proteins in neighboring cells. Furthermore, extracellular pathologic proteins have also been reported to provoke inflammatory responses that lead to neurodegeneration. Therefore, immunotherapies targeting extracellular α-synuclein and tau have been proposed as potential disease-modifying strategies. In this review, we summarize completed phase I trials and ongoing phase II trials of immunotherapies against α-synuclein and tau and further discuss concerns and hur-dles to overcome in the future.