Alpha-synuclein (phosphorylated) (p-α-syn)

Alpha-synuclein is a presynaptic protein primarily found in the central nervous system, where it plays a crucial role in regulating synaptic vesicle trafficking and neurotransmitter release (UniProt P37840). In its phosphorylated form, particularly at the Serine 129 (S129) residue, it becomes a hallmark of synucleinopathies such as Parkinson's disease and Dementia with Lewy bodies (Oueslati, 2016). While only a small fraction of alpha-synuclein is phosphorylated in healthy brains, over 90% of the protein found in Lewy bodies is phosphorylated at S129, suggesting that this modification promotes protein aggregation and neurotoxicity (Samuel et al., 2016). Therapeutic strategies targeting phosphorylated alpha-synuclein include monoclonal antibodies like Prasinezumab, designed to clear pathological aggregates, and small molecules that inhibit the kinases responsible for phosphorylation or prevent protein misfolding. Monitoring pS129 levels in biofluids or skin biopsies serves as a critical biomarker for disease progression and therapeutic efficacy in clinical trials (NIH/PubMed).

Other names

pS129 alpha-synucleinPhospho-alpha-synucleinSNCA (phosphorylated)NACP (phosphorylated)

Monoclonal antibodies target and clear extracellular alpha-synuclein aggregates to prevent cell-to-cell spread, while small molecules inhibit the aggregation of the protein or reduce its phosphorylation levels.