Pyroptosis: inflammatory cell death mechanism and its pathological roles in neurological diseases and injuries

Neurological disorders represent a major global public health challenge, causing significant impairments in motor, sensory, and cognitive functions. Among these disorders, Alzheimer’s disease, cerebrovascular diseases, and Parkinson’s disease are notably prevalent. Despite their widespread impact, effective therapeutic interventions remain limited. Recently, pyroptosis—a highly pro-inflammatory form of programmed cell death characterized by cell swelling, membrane perforation, and the release of cellular contents—has gained considerable attention. While pyroptosis plays a crucial role in host defense against pathogen infections, its excessive activation can trigger sustained inflammatory responses and has been implicated in the pathogenesis and progression of various neurological disorders. This review provides an overview of pyroptosis, including its definition, key molecular components, and associated signaling pathways, while examining its mechanistic roles in neuroinflammation, neurological disorders, cerebrovascular diseases, and neural tumors. Additionally, it explores the influence of other systemic dysregulations on the development of neurological disorders. Research has demonstrated that pyroptosis drives the death of neurons and glial cells through inflammasome activation and the Caspase-Gasdermin pathway, thereby amplifying neuroinflammation and influencing disease progression. Notably, excessive pyroptosis activation exacerbates neural damage in conditions such as Alzheimer’s disease, Parkinson’s disease, and ischemic brain injury. Consequently, targeting pyroptosis signaling pathways may present promising therapeutic strategies for neurological disorders. This review consolidates recent advancements in the field, offering valuable insights for the development of effective interventions.