Inflammasome

 Inflammasomes are cytosolic multiprotein complexes of the innate immune system responsible for the activation of inflammatory responses and cell death.[1][2] They are formed as a result of specific cytosolic pattern recognition receptors (PRRs), which are molecular sensors of microbe-derived pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs) from the host cell, or homeostatic disruptions.[1][2][3] Activation and assembly of the inflammasome promotes the activation of caspase-1, which then proteolytically cleaves pro-inflammatory cytokines, interleukin 1β (IL-1β) and interleukin 18 (IL-18), as well as the pore-forming molecule gasdermin D (GSDMD).[2][3][4] The N-terminal GSDMD fragment resulting from this cleavage induces a pro-inflammatory form of programmed cell death distinct from apoptosis, referred to as pyroptosis, which is responsible for the release of mature cytokines.[2][5] Additionally, inflammasomes can act as integral components of larger cell death-inducing complexes called PANoptosomes, which drive another distinct form of pro-inflammatory cell death called PANoptosis.[4][6]


Inflammasome formation is driven by germline-encoded PRRs, including NLRs (nucleotide-binding oligomerization domain and leucine-rich repeat-containing receptors), AIM2 (absent in melanoma 2), IFI16 (IFN-inducible protein 16), and pyrin.[2][7] Through their caspase activation and recruitment domain (CARD) or pyrin domain (PYD), the PRRs interact with the adaptor protein called apoptosis-associated speck like protein containing a CARD (also known as ASC or Pycard), which then recruits pro-caspase-1 via its CARD domain to activate inflammatory signaling and pyroptotic cell death.[2][8] Notably, the PYD of the adaptor protein ASC has been demonstrated to function as a prion-like domain, forming a self-perpetuating polymer when activated.[9] In addition to inflammasomes activating caspase-1, several studies also described non-canonical inflammasome complexes that act independently from caspase-1. In mice, the non-canonical inflammasome is activated by direct sensing of cytosolic bacterial lipopolysaccharide (LPS) by caspase-11, which subsequently induces pyroptotic cell death.[2] In human cells, the corresponding caspases of the non-canonical inflammasome are caspase 4 and caspase 5.[10][11][12][13][14]


Read more at:

https://en.wikipedia.org/wiki/Inflammasome




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