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 alpha-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 alpha-synuclein and are thus implicated in its physiological and pathological func-tions. In this review, we present (1) an overview of the pathophysiological roles of alpha-synuclein, (2) a descriptive analysis of alpha-synuclein PTMs, including phosphorylation, ubiquitination, SUMOylation, acetylation, glycation, truncation, and O-GlcNAcylation, as well as (3) a brief summary on alpha-synuclein PTMs as potential biomarkers for PD. A better understanding of alpha-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.