Emerging disease–modifying strategies targeting α–synuclein aggregation and propagation

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. The pathological hallmark of PD is loss of dopaminergic neurons in the substantia nigra and the appearance of Lewy bodies, which are mainly composed of aggregated α–synuclein (αS). Dopamine replenishment therapy can alleviate motor symptoms of PD, but there is currently no available treatment which can halt or reverse disease progression. Thus, there is an urgent need for disease modification targeting the build–up of cytotoxic αS in the nervous system. Furthermore, emerging evidence has suggested that aggregated αS can transfer from one cell to another, thereby affecting the normal physiological state of the neighboring neurons in a prion–like manner. These transmissible, extracellular αS species are ideal targets for the disease–modifying treatment including immunotherapy. In this review, I will overview the molecular structure and function of αS, its relevance to PD pathogenesis and will discuss the current status and future prospective of disease–modifying strategies targeting αS in PD.