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Fig. 10 | The Journal of Headache and Pain

Fig. 10

From: P2X7R/NLRP3 signaling pathway-mediated pyroptosis and neuroinflammation contributed to cognitive impairment in a mouse model of migraine

Fig. 10

Schematic diagram for the mechanisms of P2X7R in the regulation of inflammasome priming, activation and programmed cell death pathways in the brain following repeated dural IS stimulation. The expression of P2X7R is upregulated after repeated dural IS stimulation. P2X7R can activate the assembly of NLRP3 inflammasome, a multi-protein complex including NLRP3, adaptor (i.e., ASC) and effector proteins (i.e., total caspase-1). The formation of an inflammasome complex activates and converts total caspase-1 into active cleaved caspase-1. There are three main groups of substrates that are targeted by cleaved caspase-1. Firstly, cleaved caspase-1 can cleave both precursor IL-1β and IL-18 into active proinflammatory cytokines, mature IL-1β and IL-18. Secondly, cleaved caspase-1 can cleave GSDMD-FL into GSDMD-NT that self-oligomerize onto the plasma membrane to form a pore to facilitate the influx of water molecules to induce a lytic form of cell death known as pyroptosis. Thirdly, cleaved caspase-1 can cleave and activate total caspase-3 into cleave caspase-3 to induce apoptosis. Abbreviations: GSDMD-FL, full length Gasdermin D; GSDMD-NT, N-terminal Gasdermin D

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