Fig. 3: Crosstalk associations between the three types of PCD after stroke.
From: Targeting pyroptosis as a preventive and therapeutic approach for stroke
After stroke, TLR4/DR on the cell membrane receives the corresponding inflammatory stimulus and triggers pyroptosis, apoptosis, or necroptosis. Caspase-8 is a key protein regulating several modes of PCD death; normal expression of Caspase-8 enzyme activity favors the induction of apoptosis, diminished Caspase-8 activity helps induce necroptosis, whereas inactive Caspase-8 can promote ASC-procaspase-1 binding to induce pyroptotic cell death. The PANoptosome, a key complex triggering PAN-optosis, is mainly activated by IAV invasion, in which ZBP1 and RIPK3 act as sensors and Caspase-6 enhances their sensitivity; the reduction of TAK1 after stroke also promotes PANoptosome formation, triggering PANoptosis and aggravating brain injury. TLR4 toll-like receptor 4, DR death receptor, RIPK1 receptor interacting serine threonine kinase 1, RIPK3 receptor interacting serine threonine kinase 3, MLKL mixed-lineage kinase domain-like protein, ZBP1 Z-DNA binding protein 1, NLRP3 NOD-like receptor thermal protein domain associated protein 3, ASC apoptosis-associated speck-like protein containing CARD, NF-κB nuclear factor kappa-B, GSDMD gasdermin D, IAV influenza A virus, PANoptosis pyroptosis + apoptosis+necroptosis, TAK1 TGF beta-activated kinase 1.
