Alpha-synuclein protein (α-Synuclein (also written as αSyn or SNCA protein))

Alpha-synuclein is a small neuronal protein composed of 140 amino acids, encoded by the *SNCA* gene on chromosome 4. It is highly expressed at presynaptic terminals where it regulates synaptic vesicle trafficking, neurotransmitter release, membrane interactions, and possibly acts as a molecular chaperone during SNARE complex formation. Structurally, it is an intrinsically disordered protein, but can adopt helical conformations upon binding membranes. Its central hydrophobic region enables self-association into β-sheet-rich amyloid fibrils—a process central to the pathogenesis of several neurodegenerative diseases known collectively as synucleinopathies, including Parkinson's disease. Aggregated alpha-synuclein constitutes the main component of Lewy bodies found in affected neurons. The physiological function remains incompletely understood but includes roles in dopamine metabolism, lipid homeostasis at nerve terminals, microtubule interaction, nuclear DNA modulation, and possibly neuroprotection under certain conditions. Mutations or overexpression lead to toxic gain-of-function through aggregate formation that disrupts cellular homeostasis.

Other names

Alpha synucleinSNCA proteinNon-A beta component of AD amyloid protein (NACP)Non-A4 component of amyloid precursor proteinPARK1 proteinSYN proteinParkinson's disease familial 1 Protein

Drugs targeting alpha-synuclein generally act by: - Inhibiting misfolding/aggregation into toxic oligomers/fibrils. - Promoting clearance via immunotherapy or enhancing autophagy/proteasomal degradation pathways. - Stabilizing native conformations to prevent pathological conversion.