Synaptosomal-associated protein 25

SNAP25 (synaptosomal-associated protein 25) is a t-SNARE that plays a central role in neurotransmitter release by regulating the molecular machinery of vesicle docking and membrane fusion (UniProt: P60880). The protein also modulates plasma membrane recycling and voltage-dependent potassium channel function. It is primarily expressed in neuronal tissues where synaptic transmission occurs.

SNAP25 is associated with developmental and epileptic encephalopathy 117 (DEE117), an autosomal dominant disorder characterized by early-onset seizures, global developmental delay, intellectual disability, and variable neurological symptoms including hypotonia and movement disorders (UniProt: P60880). These findings underscore the protein's critical role in neuronal development and function.

In Alzheimer's disease, SNAP25 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.47 across multiple subcellular fractions (Chaparral AD proteomics). This reduction is consistent with synaptic dysfunction and neurodegeneration observed in AD pathology, suggesting diminished neurotransmitter release capacity in affected neurons.