Syntaxin1A in synaptopathies: From molecular mechanisms to therapeutic implications in neurological disorders (Review).

Syntaxin1A (STX1A) is a presynaptic membrane protein that is abundantly expressed in the central nervous system. It is a key member of the soluble N-ethylmaleimide sensitive factor attachment protein receptor protein family. Notably, STX1A acts as a 'molecular hub' in neural networks by regulating presynaptic membrane fusion with synaptic vesicles and the subsequent release of neurotransmitters. In addition to this function, STX1A is crucial for neuronal development, synaptic plasticity, and ion channel regulation. The deficiency or variation of STX1A not only directly disrupts neurotransmitter transmission but also contributes to pathological processes in neurological disorders such as Alzheimer's disease, epilepsy, autism spectrum disorder, and ischemic stroke by interfering with excitatory-inhibitory balance, inducing neuroinflammation, and triggering neuronal apoptosis. The present review summarizes the structure and physiological functions of STX1A, highlights its mechanisms in the pathogenesis of various neurological diseases, and examines its potential as a diagnostic biomarker and therapeutic target for these diseases.