Chemical Modulation of Gasdermin-Mediated Pyroptosis and Therapeutic Potential. Issue 4 (28th February 2022)

• Record Type: Journal Article
• Authors: Ryder, Christopher B.; Kondolf, Hannah C.; O'Keefe, Meghan E.; Zhou, Bowen; Abbott, Derek W.
• Is Part Of: Journal of molecular biology. Volume 434:Issue 4(2022)
• Publication Date: 2022-02-28
• Subjects: inflammasome -- inflammasomopathy -- immunogenic cell death -- anti-tumor immunity -- pore-forming protein; AML Acute myeloid leukemia -- ASC Apoptosis-associated speck-like protein containing a CARD -- CAPS Cryopyrin-associated periodic syndrome -- CAR Chimeric antigen receptor -- CARD Caspase activation and recruitment domain -- CHIP Clonal hematopoiesis of indeterminate potential -- CRS Cytokine release syndrome -- CT C-terminal/C-terminus -- CTL Cytotoxic T lymphocyte -- DAMP Danger-associated molecular pattern -- DIC Disseminated intravascular coagulation -- DMF Dimethylfumarate -- DPP9 Dipeptidyl peptidase 9 -- ds Double-stranded -- DSF Disulfiram -- EAE Experimental autoimmune encephalitis -- ELANE Neutrophil elastase -- ESCRT Endosomal sorting complex required for transport -- FCAS Familial cold auto-inflammatory syndrome -- FIIND 'Function to find' domain -- FKLC Familial keratosis lichenoides chronica -- FMF Familial Mediterranean fever -- GSDM Gasdermin -- IBD Inflammatory bowel disease -- ICD Immunogenic cell death -- JRRP Juvenile recurrent respiratory papillomatosis -- MDS Myelodysplastic syndrome -- MLKL Mixed-lineage kinase domain-like -- MS Multiple sclerosis -- MSPC Multiple self-healing palmoplantar carcinoma -- NET Neutrophil extracellular trap -- NLR Nucleotide-binding domain (NBD), leucine-rich repeat (LRR)-containing -- NOMID Neonatal-onset multisystem inflammatory disorder -- NSA Necrosulfonamide -- NT N-terminal/N-terminus -- PLC Phospholipase C -- PTM Post-translational modification -- PYD Pyrin domain; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2021.167183
• Languages: English
• ISSNs: 0022-2836

Abstract

Graphical abstract: Highlights: Gasdermins are critical effectors of inflammatory mediator release and pyroptosis. Gasdermins sit as a bottleneck between diverse upstream stimuli and effector release. This central position makes gasdermins prime targets for a variety of human diseases. Here we discuss the known function and regulation of gasdermins in human disease. We also describe strategies to target gasdermin-mediated pyroptosis therapeutically. Abstract: Pyroptosis, a lytic form of programmed cell death, both stimulates effective immune responses and causes tissue damage. Gasdermin (GSDM) proteins are a family of pore-forming executors of pyroptosis. While the most-studied member, GSDMD, exerts critical functions in inflammasome biology, emerging evidence demonstrates potential broad relevance for GSDM-mediated pyroptosis across diverse pathologies. In this review, we describe GSDM biology, outline conditions where inflammasomes and GSDM-mediated pyroptosis represent rational therapeutic targets, and delineate strategies to manipulate these central immunologic processes for the treatment of human disease.