Inflammasomes − Caspase-1 Activation Scaffolds

An inflammasome represents a high molecular weight complex that activates inflammatory caspases and activates cytokines of the IL-1 family. Several inflammasomes have been described and were so far defined by the NLR protein that they contain - the NLRP1 (NALP1) inflammasome, the NLRP3 (NALP3) inflammasome and the IPAF (NLRC4) inflammasome. Interestingly, the AIM2 (absent in melanoma 2) inflammasome, which has been described recently, does not contain any member of the NLR family. Inflammasomes can be activated through multiple signals including live bacteria, microbial toxins, xeno-compounds, PAMPs and DAMPs. It is suggested that the LRR domains of NLRP3 mediate autorepression, probably by SGT1 and HSP90 chaperones that maintain NLRP3 in an inactive, but signal-competent state. Upon sensing of their respective ligands, NLRP1 or NLRP3 oligomerize via the NACHT domain, what leads to PYD clustering and to the recruitment of the adapter protein ASC (apoptosis-associated speck-like protein containing a CARD) due to homotypic PYD-PYD interactions. In the case of AIM2, oligomerization is likely mediated by clustering upon multiple binding sites within dsDNA and not by a central oligomerization domain like NACHT. 

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