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. Author manuscript; available in PMC: 2023 Apr 1.
Published in final edited form as: Pharmacol Ther. 2021 Oct 4;232:108010. doi: 10.1016/j.pharmthera.2021.108010

Figure 4: Targeting PANoptotic regulation of inflammatory cell death.

Figure 4:

Activation of an apical sensor, such as Z-DNA-binding protein 1 (ZBP1), induces formation of a PANoptosome complex containing key pyroptotic, apoptotic, and necroptotic molecules. Assembly of the PANoptosome leads to the induction of three arms of cell death, executed by members of the gasdermin (GSDM) family of proteins, caspase-3/7, and MLKL. Inhibition of PANoptosis or PANoptosis-induced inflammation can occur at a number of levels. Direct blockade of sensor molecules, such as ZBP1, could block formation of the PANoptosome and induction of PANoptosis. Inhibition of scaffolding or enzymatic molecules could alter the activity and composition of the PANoptosome, while inhibition of specific executioners of one arm of cell death can drive death into a different arm of PANoptosis. An alternative approach is the blockade of downstream inflammatory signaling molecules, such as IL-1.