NLR family CARD domain-containing protein 4 and Absent in melanoma 2 inflammasome complexes (NLRC4/AIM2 inflammasome)

The NLRC4 and AIM2 inflammasome complexes are critical components of the innate immune system that function as intracellular sensors for pathogens and cellular stress. NLRC4 (NLR family CARD domain-containing protein 4) is primarily activated by bacterial components such as flagellin and type III secretion system (T3SS) proteins, while AIM2 (Absent in melanoma 2) recognizes double-stranded DNA (dsDNA) from both viral and bacterial sources. Upon activation, these proteins recruit the adapter protein ASC and the protease Caspase-1 to form a large multiprotein complex, leading to the maturation of pro-inflammatory cytokines IL-1beta and IL-18 and the induction of pyroptosis, a form of programmed inflammatory cell death. Dysregulation of these complexes is linked to severe autoinflammatory conditions, such as NLRC4-associated macrophage activation syndrome (MAS), and plays a role in the progression of various cancers and autoimmune disorders. Therapeutic strategies targeting these complexes often focus on inhibiting Caspase-1 or blocking the downstream effects of the released cytokines to mitigate chronic inflammation.

Other names

IPAF (ICE protease-activating factor)CLANPYHIN4Absent in melanoma 2NLR family CARD domain-containing protein 4NLRC4-AIM2 supramolecular complex

Inhibition of Caspase-1 activity, prevention of ASC speck formation, or blockade of downstream pro-inflammatory cytokines (IL-1beta and IL-18).