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Inflammasome activation and regulation: toward a better understanding of complex mechanisms | Cell Discovery
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Inflammasomes are cytoplasmic multiprotein complexes comprising a sensor protein, inflammatory caspases, and in some but not all cases an adapter protein connecting the two. They can be activated by a repertoire of endogenous and exogenous stimuli, leading to enzymatic activation of canonical caspase-1, noncanonical caspase-11 (or the equivalent caspase-4 and caspase-5 in humans) or caspase-8, resulting in secretion of IL-1β and IL-18, as well as apoptotic and pyroptotic cell death. Appropriate inflammasome activation is vital for the host to cope with foreign pathogens or tissue damage, while aberrant inflammasome activation can cause uncontrolled tissue responses that may contribute to various diseases, including autoinflammatory disorders, cardiometabolic diseases, cancer and neurodegenerative diseases. Therefore, it is imperative to maintain a fine balance between inflammasome activation and inhibition, which requires a fine-tuned regulation of inflammasome assembly and effector function. Recently, a growing body of studies have been focusing on delineating the structural and molecular mechanisms underlying the regulation of inflammasome signaling. In the present review, we summarize the most recent advances and remaining challenges in understanding the ordered inflammasome assembly and activation upon sensing of diverse stimuli, as well as the tight regulations of these processes. Furthermore, we review recent progress and challenges in translating inflammasome research into therapeutic tools, aimed at modifying inflammasome-regulated human diseases.
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pubmed, inflammasome, nlrp, article, scholar, google, cas, activation, central, caspase, cell, inflammasomes, aim, nlrc, protein, signaling, pyrin, immunol, assembly, immune, asc, nat, nature, regulation, human, inflammation, innate, mechanisms, dna, inflammatory, noncanonical, domain, infection, host, immunity, ilβ, activity, bacterial, studies, nlrpb, cells, apoptosis, including, disease, pyroptosis, intestinal, mice, regulates, death, response,
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nature portfolio privacy policy intrinsic “nf-κb-p62-mitophagy” pathway ketone body beta-hydroxy-butirate advertising therapeutic tools asc-mediated nuclear-factor-kappa enhancing tlr-4–trif–ifnar signaling crystal-induced il-1β secretion278 iapp‐induced il‐1β production social media trif/ripk1/fadd-dependent pathways ketone body β-hydroxybutyrate mitosis-related serine-threonine kinase transcription factor nf-kappab reprints pore-induced intracellular traps microrna-based post-transcriptional control beta-sulfonyl nitrile compound nlrp3-mediated il-1beta activation short double-stranded rna tlr4-independent endotoxic shock mir-122-5p/brcc3 axis free cytosolic double-stranded deubiquitinating enzyme brca1/brca2 double-stranded dna backbone nlrp3 il-1/il-18 axis noncanonical nf-kappab signaling multi-factorial diseases involving hepatic ischemia/reperfusion injury173 caspase-1 cleaves pro-il-1β urate crystal-induced peritonitis nf-κb-mediated expression bone marrow-derived cells210 sesn2/sestrin2 suppresses sepsis extreme c-terminal side ischemia–reperfusion injured myocardium144 irf1-directed antiviral responses gsdma-induced cell death33 crystal-induced nlrp3 responses golgi-mediated protein kinase drive anti-viral responses central nervous system volume-regulated anion channels sun yat‐sen university sun yat-sen university inflammasome-dependent immune responses ischemia-reperfusion injured heart low-grade inflammation sustained trans-golgi network
Questions {❓}
- Mitochondrial DNA signals driving immune responses: Why, How, Where?
- NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production?
- The HIN-200 family: more than interferon-inducible genes?
- What role does pyroptosis play in microbial infection?
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