Abstract
The NLRP3 inflammasome is a core component of innate immunity, and dysregulation of NLRP3 inflammasome involves developing autoimmune, metabolic, and neurodegenerative diseases. Potassium efflux has been reported to be essential for NLRP3 inflammasome activation by structurally diverse pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). Thus, the molecular mechanisms underlying potassium efflux to activate NLRP3 inflammasome are under extensive investigation. Here, we review current knowledge about the distinction channels or pore-forming proteins underlying potassium efflux for NLRP3 inflammasome activation with canonical/non-canonical signaling or following caspase-8 induced pyroptosis. Ion channels and pore-forming proteins, including P2X7 receptor, Gasdermin D, pannexin-1, and K2P channels involved present viable therapeutic targets for NLRP3 inflammasome related diseases.
Highlights
Given the critical role of NLRP3 inflammasome in autoimmune, metabolic, and neurodegenerative diseases and the essential role of potassium efflux in NLRP3 inflammasome activation, it is of great significance to explore the molecular mechanisms underlying potassium efflux during NLRP3 inflammasome activation under different circumstances
The important role of the P2X7 receptor and GSDMD in immune responses has gained a lot of attention, both academically and industrially [31, 34]
Crystalline substances depend on potassium efflux to activate NLRP3 inflammasome, this process’s mechanism is not clear and needed to be resolved in the future
Summary
Received: 23 September 2020 Accepted: 09 November 2020 Published: 07 December 2020. Citation: Xu Z, Chen Z-m, Wu X, Zhang L, Cao Y and Zhou P (2020) Distinct Molecular. We review current knowledge about the distinction channels or pore-forming proteins underlying potassium efflux for NLRP3 inflammasome activation with canonical/non-canonical signaling or following caspase-8 induced pyroptosis. The activation process of NLRP3 inflammasome could be provided by surprisingly various types of PAMPs (pathogen-associated molecular pattern) or DAMPs (danger-associated molecular pattern) These include extracellular ATP, pore-forming toxins (nigericin and maitotoxin, etc.), particulate matter (urate crystalline MSU, aluminum adjuvant, silica, and asbestos), and misfolded proteins related to neurodegenerative diseases (fibrillar Ab protein; a-synuclein) [10,11,12]. It was reported that the activated caspase-11 cleaves pannexin-1 followed up by ATP release, which in turn activates the P2X7 receptor to mediate potassium efflux and NLRP3 inflammasome activation [39]. This study is contradicted with studies by several other groups that we will discuss
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