The phosphorylation of α-synuclein: development and implication for the mechanism and therapy of the Parkinson's disease

Parkinson's disease (PD) is cited to be the second most common neuronal degenerative disorders; however, the exact mechanism of PD is still unclear. α-synuclein is one of the key proteins in PD pathogenesis as it's the main component of the PD hallmark Lewy bodies (LBs). Nowadays, the study of α-synuclein phosphorylation mechanism related to the PD pathology has become a research hotspot, given that 90% of α-synuclein deposition in LBs is phosphorylated at Ser129, whereas in normal brains, only 4% or less of α-synuclein is phosphorylated at the residue. Here, we review the related study of PD pathological mechanism involving the phosphorylation of α-synuclein mainly at Ser129, Ser87, and Tyr125 residues in recent years, as well as some explorations relating to potential clinical application, in an attempt to describe the development and implication for the mechanism and therapy of PD. Given that some of the studies have yielded paradoxical results, there is need for more comprehensive research in the field. The phosphorylation of α-synuclein might provide a breakthrough for PD mechanism study and even supply a new therapeutic strategy. The milestone study on the phosphorylation of α-synuclein mainly at Ser129, Ser87, and Tyr125 relating to PD in recent years as well as some clinical application exploration are overviewed. The potential pathways of the phosphorylated α-synuclein related to PD are also summarized. The review may supply more ideas and thinking on this issue for the scientists in related research field.