Necroptosis and inflammasome pathway

The necroptosis and inflammasome pathways are interconnected mechanisms of programmed cell death and pro-inflammatory signaling that play critical roles in the innate immune system (PMID: 32024971). Necroptosis is a form of regulated necrosis mediated by the RIPK1-RIPK3-MLKL signaling axis, often triggered when apoptosis is inhibited (PMID: 28416233). The inflammasome is a multi-protein complex, most notably NLRP3, that activates Caspase-1 to process pro-inflammatory cytokines like IL-1β and IL-18 and induce pyroptosis via gasdermin D (PMID: 31043709). These pathways frequently exhibit crosstalk, sometimes collectively termed PANoptosis, where the inhibition of one can trigger the activation of the other (PMID: 33547302). Dysregulation of these processes is linked to a wide range of inflammatory, autoimmune, and neurodegenerative diseases (PMID: 30275444). Therapeutic strategies focus on inhibiting specific kinases or scaffold proteins within these pathways to dampen excessive inflammation and tissue damage (PMID: 31636403).

Other names

PANoptosisProgrammed necrosis and inflammasome signalingRIPK-dependent cell death and NLRP3 signaling

Drugs targeting this pathway typically inhibit key signaling nodes such as Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) or 3 (RIPK3) to block necroptosis, or inhibit the NLRP3 inflammasome complex and Caspase-1 to prevent the maturation of pro-inflammatory cytokines and pyroptotic cell death (PMID: 31636403, PMID: 31043709).