Alpha-synuclein

Alpha-synuclein (SNCA) is a 140-amino-acid neuronal protein that regulates synaptic vesicle trafficking and neurotransmitter release (UniProt: P37840). As a monomer, it enhances vesicle priming, fusion, and exocytotic pore dilation by increasing local Ca²⁺ release. In its multimeric membrane-bound state, it functions as a molecular chaperone, assisting in SNARE-complex assembly at the presynaptic plasma membrane, a function critical for sustained synaptic integrity during aging. Alpha-synuclein also modulates dopamine neurotransmission through interaction with the dopamine transporter.

Alpha-synuclein is implicated in several neurodegenerative conditions, most notably Parkinson disease (PARK1, PARK4) and Dementia with Lewy bodies (DLB), where pathologic aggregation of the protein into Lewy bodies is a hallmark feature (UniProt: P37840).

In Alzheimer's Disease, alpha-synuclein is downregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). Across the measured subcellular fractions, the protein showed a mean log2 fold-change of −0.47, indicating modest but consistent reduction in AD pathology.