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Fig. 1 | Journal of Neuroinflammation

Fig. 1

From: More than just inflammation: Ureaplasma species induce apoptosis in human brain microvascular endothelial cells

Fig. 1

Different forms of programmed cell death and associated cascades. This simplified scheme describes different forms of programmed cell death and the respective key mediators [28,29,30, 48, 52]. Pyroptosis—bacteria or bacterial components usually employ toll like receptor (TLR) signaling and recruit caspase (CASP) 4 and 5 or CASP1 via inflammasomes, including NOD-like receptor pyrin domain-containing (NLRP) 3. Caspase-driven cleavage of gasdermin D induces membrane rupture and pyroptosis. Necroptosis—DNA or RNA fragments are recognized by Z-DNA binding protein (ZBP) 1 or TLR, which signal via receptor-interacting protein kinase (RIPK) 1. Tumor necrosis factor (TNF) signaling through TNF receptor (TNFR) 1 also involves RIPK1. ZBP1 or RIPK1 activates RIPK3, resulting in recruitment and phosphorylation of mixed lineage kinase-domain-like (MLKL), which ultimately induces pore formation and necroptosis. Apoptosis—lymphocytes, natural killer (NK) cells, or DNA damage (via p53) induce B cell lymphoma (BCL) 2 associated X apoptosis regulator (BAX) or BCL2 homologous antagonist/killer (BAK). BAX and BAK permeabilize the mitochondrial membrane and consecutively released cytochrome C (CytC) binds to apoptotic protease activating factor (APAF) 1, thus forming the apoptosome which activates CASP9. CASP9 activates CASP3 and 7, thereby inducing apoptosis (intrinsic pathway). Inflammatory cells may also directly activate CASP 3 and 7. In an extrinsic apoptosis pathway, first apoptosis signal ligand (FASL) is recruited by immune cells or Fos proto-oncogene (FOS) and activates CASP8 via FAS-associated death domain (FADD). CASP8 then activates CASP 3 and 7. All three processes are closely interacting and are additionally regulated by numerous anti-apoptotic, anti-pyroptotic, and anti-necroptotic proteins not listed here. ├ inhibit / downregulate; ← activate / upregulate / employ. Illustrations: https://smart.servier.com/

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