1. Role of pyroptosis in spinal cord injury and its therapeutic implications
- Author
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Chang Jia, Jian Xiao, Abdullah Al Mamun, Fahad Munir, Ilma Monalisa, Kailiang Zhou, and Yanqing Wu
- Subjects
0301 basic medicine ,CO, Carbon monoxide ,Nrf2, Nuclear factor erythroid 2-related factor 2 ,IL-1β, Interleukin-1 beta ,H2O2, Hydrogen peroxide ,CCK-8, Cell Counting Kit-8 ,0302 clinical medicine ,Neuroinflammation ,Medicine ,LPS, Lipopolysaccharide ,JOA, Japanese orthopedics association ,lcsh:R5-920 ,Multidisciplinary ,Pyroptosis ,Inflammasome ,GSDMD, Gasdermin D ,PRRs, Pattern recognition receptors ,030220 oncology & carcinogenesis ,Caspase-1 ,ATP, Adenosine triphosphate ,DAMPs, Damage-associated molecular patterns ,Signal transduction ,HO-1, Heme oxygenase-1 ,lcsh:Medicine (General) ,Intracellular ,ECH, Echinacoside ,medicine.drug ,ASC, apoptosis-associated speck-like protein ,Therapeutic implications ,Programmed cell death ,PAMPs, Pathogen-associated molecular patterns ,CORM-3, Carbon monoxide releasing molecle-3 ,Caspase 1 ,Spinal cord injury ,CNS, central nervous system ,Article ,IL-18, Interleukin-18 ,03 medical and health sciences ,NLRP3 ,OPCs, Oligodendrocyte progenitor cells ,lcsh:Science (General) ,ComputingMethodologies_COMPUTERGRAPHICS ,DRD1, Dopamine Receptor D1 ,business.industry ,Mechanism (biology) ,Cx43, Connexin 43 ,NLRP1, NOD-like receptor protein 1 ,BBG, Brilliant blue G ,TLR4, Toll-like receptor 4 ,NF-κB, Nuclear factor-kappa B ,NLRP1b, NOD-like receptor protein 1b ,Gal-3, Galectin-3 ,AIM2, Absent in melanoma 2 ,IRE1, Inositol requiring enzyme 1 ,030104 developmental biology ,NDI, Neck data index ,double stranded DNAIR, Ischemia reperfusion ,si-RNA, Small interfering RNA ,NLRP3, Nucleotide-binding domain-like receptor protein 3 ,business ,Neuroscience ,ROS, Reactive oxygen species ,TXNIP, Thioredoxin-interacting protein ,lcsh:Q1-390 - Abstract
Graphical abstract, Highlights • Neuroinflammation plays a key role in the secondary injury of acute SCI. • Pyroptosis is defined as a newly programmed cell death. • Recent studies show that pyroptosis play a key role in SCI. • Some molecules can significantly inhibit pyroptosis process in SCI. • Targeting pyroptosis and inflammasome components can be novel therapeutic strategies for SCI., Background Currently, spinal cord injury (SCI) is a pathological incident that triggers several neuropathological conditions, leading to the initiation of neuronal damage with several pro-inflammatory mediators' release. However, pyroptosis is recognized as a new programmed cell death mechanism regulated by the stimulation of caspase-1 and/or caspase-11/-4/-5 signaling pathways with a series of inflammatory responses. Aim Our current review concisely summarizes the potential role of pyroptosis-regulated programmed cell death in SCI, according to several molecular and pathophysiological mechanisms. This review also highlights the targeting of pyroptosis signaling pathways and inflammasome components and its therapeutic implications for the treatment of SCI. Key scientific concepts Multiple pieces of evidence have illustrated that pyroptosis plays significant roles in cell swelling, plasma membrane lysis, chromatin fragmentation and intracellular pro-inflammatory factors including IL-18 and IL-1β release. In addition, pyroptosis is directly mediated by the recently discovered family of pore-forming protein known as GSDMD. Current investigations have documented that pyroptosis-regulated cell death plays a critical role in the pathogenesis of multiple neurological disorders as well as SCI. Our narrative article suggests that inhibiting the pyroptosis-regulated cell death and inflammasome components could be a promising therapeutic approach for the treatment of SCI in the near future.
- Published
- 2021