Synaptosomal-associated protein 25 (SNAP-25) (SNAP-25)

Synaptosomal-associated protein 25 (SNAP-25) is a critical component of the SNARE (Soluble NSF Attachment Protein Receptor) complex, which mediates the fusion of synaptic vesicles with the presynaptic plasma membrane. Located primarily on the cytosolic face of the plasma membrane in nerve terminals, SNAP-25 contributes two alpha-helices to the four-helix bundle of the SNARE complex, working alongside syntaxin-1 and synaptobrevin-2 to facilitate calcium-triggered neurotransmitter exocytosis (UniProt P60880). In cholinergic presynaptic terminals, SNAP-25 is the specific molecular target of Botulinum neurotoxin type A (BoNT/A). The toxin enters the neuron and its light chain proteolytically cleaves SNAP-25 near the C-terminus, rendering it unable to form a functional SNARE complex (StatPearls, Botulinum Toxin). This action effectively blocks the release of acetylcholine into the neuromuscular junction, leading to localized muscle paralysis. This mechanism is widely utilized in clinical practice to treat conditions such as cervical dystonia, blepharospasm, chronic migraine, and various forms of muscle spasticity (PubMed PMC3022451). Beyond its role in the peripheral nervous system, SNAP-25 is also essential for central neurotransmission, and its dysfunction or genetic variation has been linked to neuropsychiatric and neurodevelopmental disorders including schizophrenia and ADHD (PubMed PMC2824144).

Other names

SNAP25Synaptosomal-associated 25 kDa proteinSuperproteinSUPRIC-4

Proteolytic cleavage of SNAP-25 by the light chain of Botulinum neurotoxin type A, which prevents the formation of the SNARE complex and inhibits the release of acetylcholine.