The role of pyroptosis in cognitive impairment

Abstract

Cognitive impairment is a major global disease, manifests as a decline in cognitive functioning and endangers the health of the population worldwide. The incidence of cognitive impairment has increased rapidly with an increasingly aging population. Although the mechanisms of cognitive impairment have partly been elucidated with the development of molecular biological technology, treatment methods are very limited. As a unique form of programmed cell death, pyroptosis is highly pro-inflammatory and is closely associated with the incidence and progression of cognitive impairment. In this review, we discuss the molecular mechanisms of pyroptosis briefly and the research progress on the relationship between pyroptosis and cognitive impairment and its potential therapeutic values, to provide a reference for research in the field of cognitive impairment.

NLRP3 inflammasome in cognitive impairment and pharmacological properties of its inhibitors

“…Although the role and the mechanism of pyroptosis in cognitive dysfunction are not fully understood, studies have shown that P2X7R/NLRP3, NLRP3/caspase-1, NLRP3/caspase-1/gasdermin D (GSDMD) and other signaling pathways related to pyroptosis are involved in the occurrence and development of cognitive dysfunction with different causes [ 72 – 74 ]. In patients with cognitive impairment, the levels of pyroptosis signaling pathways are significantly upregulated, accompanied by release of a large number of inflammatory substances (such as IL-1β and IL-18), leading to an inflammatory response cascade that further causes damage to brain tissues [ 72 ].…”

“…Cerebrovascular disease is also a major cause of cognitive impairment. It includes acute ischemic stroke and chronic cerebral hypoperfusion (CCH) [ 72 ]. The acute ischemic stroke is caused by the sudden interruption or reduction of the local blood supply to the brain, which often occurs in conjunction with pre-existing microvascular and neurodegenerative changes, leading to disrupted energy supply, toxicity of excitatory glutamate, neuronal death, and cognitive dysfunction [ 94 ].…”