Targeting α-synuclein post-translational modifications in Parkinson’s disease

Parkinson’s disease (PD) is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the nigrostriatal pathway. Although the exact mechanisms underlying PD are still not completely understood, it is well accepted that α-synuclein plays key pathophysiological roles as the main constituent of the cytoplasmic inclusions known as Lewy bodies. Several post-translational modifications (PTMs), such as the best-known phosphorylation, target α-synuclein and are thus implicated in its physiological and pathological functions. In this review, we present (1) an overview of the pathophysiological roles of α-synuclein, (2) a descriptive analysis of α-synuclein PTMs, including phosphorylation, ubiquitination, SUMOylation, acetylation, glycation, truncation, and O-GlcNAcylation, as well as (3) a brief summary on α-synuclein PTMs as potential biomarkers for PD. A better understanding of α-synuclein PTMs is of paramount importance for elucidating the mechanisms underlying PD and can thus be expected to improve early detection and monitoring disease progression, as well as identify promising new therapeutic targets.