An emerging role of SNAREs in ischemic stroke: From pre-to post-diseases

Ischemic stroke is a debilitating condition characterized by high morbidity, disability, recurrence, and mortality rates on a global scale, posing a significant threat to public health and economic stability. Extensive research has thoroughly explored the molecular mechanisms underlying ischemic stroke, elucidating a strong association between soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor proteins (SNAREs) and the pathogenesis of this condition. SNAREs, a class of highly conserved proteins involved in membrane fusion, play a crucial role in modulating neuronal information transmission and promoting myelin formation in the central nervous system (CNS). Preventing the SNARE complex formation, malfunctions in SNARE-dependent exocytosis, and altered regulation of SNARE-mediated vesicle fusion are linked to excitotoxicity, endoplasmic reticulum (ER) stress, and programmed cell death (PCD) in ischemic stroke. However, its underlying mechanisms remain unclear. This study conducts a comprehensive review of the existing literature on SNARE proteins, encompassing the structure, classification, and expression of the SNARE protein family, as well as the assembly - disassembly cycle of SNARE complexes and their physiological roles in the CNS. We thoroughly examine the mechanisms by which SNAREs contribute to the pathological progression and associated risk factors of ischemic stroke (hypertension, hyperglycemia, dyslipidemia, and atherosclerosis). Furthermore, our findings highlight the promise of SNAREs as a viable target for pharmacological interventions in the treatment of ischemic stroke.