Role of pyroptosis in spinal cord injury and its therapeutic implications

• Published in: Journal of advanced research Vol. 28; pp. 97 - 109
• Main Authors: Al Mamun, Abdullah, Wu, Yanqing, Monalisa, Ilma, Jia, Chang, Zhou, Kailiang, Munir, Fahad, Xiao, Jian
• Format: Journal Article
• Language: English
• Published: Egypt Elsevier B.V 01-02-2021; Elsevier
• Subjects: Caspase-1; Neuroinflammation; NLRP3; Pyroptosis; Spinal cord injury; Therapeutic implications; Therapeutic implications; PRRs; BBG; CNS; HO-1; double stranded DNAIR; H2O2; Spinal cord injury; LPS; Gal-3; DAMPs; Caspase-1; ASC; NF-κB; NDI; OPCs; si-RNA; Nrf2; IRE1; NLRP3; PAMPs; CCK-8; CORM-3; NLRP1; DRD1; JOA; GSDMD; NLRP1b; Pyroptosis; Neuroinflammation; ECH; IL-1β; CO; AIM2; Cx43; IL-18; ROS; TXNIP; ATP; TLR4; IL-18, Interleukin-18; double stranded DNAIR, Ischemia reperfusion; JOA, Japanese orthopedics association; IRE1, Inositol requiring enzyme 1; BBG, Brilliant blue G; CCK-8, Cell Counting Kit-8; Nrf2, Nuclear factor erythroid 2-related factor 2; HO-1, Heme oxygenase-1; NLRP1, NOD-like receptor protein 1; PAMPs, Pathogen-associated molecular patterns; GSDMD, Gasdermin D; CORM-3, Carbon monoxide releasing molecle-3; NDI, Neck data index; LPS, Lipopolysaccharide; si-RNA, Small interfering RNA; IL-1β, Interleukin-1 beta; NLRP3, Nucleotide-binding domain-like receptor protein 3; ATP, Adenosine triphosphate; TLR4, Toll-like receptor 4; ASC, apoptosis-associated speck-like protein; OPCs, Oligodendrocyte progenitor cells; H2O2, Hydrogen peroxide; NF-κB, Nuclear factor-kappa B; CNS, central nervous system; Cx43, Connexin 43; CO, Carbon monoxide; ROS, Reactive oxygen species; ECH, Echinacoside; Gal-3, Galectin-3; DRD1, Dopamine Receptor D1; DAMPs, Damage-associated molecular patterns; AIM2, Absent in melanoma 2; NLRP1b, NOD-like receptor protein 1b; PRRs, Pattern recognition receptors; TXNIP, Thioredoxin-interacting protein
• ISSN: 2090-1232; 2090-1224
• DOI: 10.1016/j.jare.2020.08.004

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•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.
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.
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.
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.