Alpha-synuclein (SNCA)

Alpha-synuclein (SNCA) is an abundant neuronal protein essential for proper synaptic function, especially at presynaptic terminals in the brain, where it regulates synaptic vesicle trafficking and neurotransmitter (notably dopamine) release. While its precise physiological role remains partially understood, alpha-synuclein is implicated in synaptic plasticity, maintenance of synaptic vesicle pools, microtubule transport, and DNA repair processes. Pathologically, SNCA gene mutations, multiplications, or dysregulated expression cause misfolding and toxic aggregation of alpha-synuclein (as Lewy bodies), which underlies the pathogenesis of Parkinson's disease, multiple system atrophy, and other synucleinopathies. SNCA is therefore a central target for neurodegenerative disease-modifying therapies, with efforts underway to reduce its expression or aggregation to slow disease progression. Safety challenges for SNCA-targeting therapies include disruption of normal neuronal physiology and risk of immunologic or cognitive adverse effects.

Other names

Synuclein alphaNACPNonA-beta component of AD amyloidPARK1PARK4PD1Synuclein, alpha (non A4 component of amyloid precursor)SYUA_HUMAN

Reducing or silencing SNCA gene expression (antisense oligonucleotides); Immunotherapy (clearance of extracellular/aggregated alpha-synuclein); Inhibition of SNCA aggregation or misfolding; Modulation of SNCA-related signaling pathways (e.g., mitochondrial protection, anti-inflammatory activity).