The role of Nod-like receptor protein 3 inflammasome activated by ion channels in multiple diseases

Abstract

The inflammasome is a multimeric protein complex located in the cytoplasm that is activated by many factors and subsequently promotes the release of proinflammatory factors such as interleukin (IL)-1β and IL-18, resulting in a series of inflammatory responses that ultimately lead to the occurrence of various diseases. The Nod-like receptor protein 3 (NLRP3) inflammasome is the most characteristic type and the most widely studied among many inflammasomes. Activation of the NLRP3 inflammasome is closely related to the occurrence of many diseases, such as Alzheimer's disease. At present, a large number of studies have focused on the mechanisms underlying the activation of the NLRP3 inflammasome. Plenty of articles have reported the activation of the NLRP3 inflammasome by various ions, such as K+ and Na+ reflux and Ca2+ influx. However, few articles have reviewed the effects of various ion channels on the activation of the NLRP3 inflammasome and the relationship between the diseases caused by these proteins. This article mainly summarizes the relationship between intracellular and extracellular ion activities and ion channels and the activation of the NLRP3 inflammasome. We also provide a general summary of the diseases of each system caused by NLRP3 activation. We hope that more research will provide options for the treatment of diseases driven by the NLRP3 inflammasome.

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“…The NOD-like receptor signaling pathway, particularly the NLRP3 inflammasome, promotes the release of proinflammatory cytokines such as IL-1β and IL-18, exacerbating neuroinflammation and contributing to AD progression 69 . This pathway is further activated by dysregulated ions like K+ and Ca2+, prevalent in AD, which heightens the inflammatory response 69 . TLR signaling, notably through TLR3 and TLR4, influences Aβ dynamics and mediates neuroinflammation.…”