Necroptosis in vascular cognitive impairment: mechanisms and therapeutic potential

Cerebral ischemia and hypoxia play key roles in the occurrence and development of vascular cognitive impairment (VCI). However, the pathophysiology of VCI remains unclear. Necroptosis is a non-cysteine-dependent form of cell death mediated by serine/threonine kinases receptor-interacting protein kinase-1 and -3 and mixed lineage kinase domain-like protein. A search of PubMed and Web of Science was conducted using terms related to VCI and necroptosis. Necroptosis is important in neuroinflammation, neuronal loss, blood-brain barrier dysfunction, and demyelination. Cerebral ischemia activates the necroptotic pathway, and necroptosis inhibitors have a significant inhibitory effect on brain injury. This review focuses on the pathogenesis of VCI and clarifies the core regulatory mechanism of necroptosis in vascular dementia, which lays a scientific foundation for cognitive impairment prevention and treatment by targeting necroptosis in VCI.