Role of Pyroptosis in Spinal Cord Injury and Its Therapeutic Implications

Overview

Journal J Adv Res

Specialties General Medicine
Science

Date 2020 Dec 28

PMID 33364048

Citations 75

Authors

Abdullah Al Mamun

Yanqing Wu

Ilma Monalisa

Chang Jia

Kailiang Zhou

Fahad Munir

Jian Xiao

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

FOXO3-induced microRNA-128-3p promotes the progression of spinal cord injury in mice via regulating NLRP3 inflammasome-mediated pyroptosis.

Yang S, Guan Y, Zheng C, Xia X, Ma X, Jiang J Front Immunol. 2025; 16:1526721.

PMID: 40061945 PMC: 11885150. DOI: 10.3389/fimmu.2025.1526721.

Macrophage polarization-related gene SOAT1 is involved in inflammatory response and functional recovery after spinal cord injury.

Peng P, Wang H, Pang Z, Zhang H, Hu S, Ma X Mol Cell Biochem. 2025; .

PMID: 40050510 DOI: 10.1007/s11010-025-05246-7.

Bioinformatics analysis of genes associated with disulfidptosis in spinal cord injury.

Wang S, Liu X, Tian J, Liu S, Ke L, Zhang S PLoS One. 2025; 20(2):e0318016.

PMID: 39951434 PMC: 11828381. DOI: 10.1371/journal.pone.0318016.

Long-read sequencing of 945 Han individuals identifies structural variants associated with phenotypic diversity and disease susceptibility.

Gong J, Sun H, Wang K, Zhao Y, Huang Y, Chen Q Nat Commun. 2025; 16(1):1494.

PMID: 39929826 PMC: 11811171. DOI: 10.1038/s41467-025-56661-9.

HSPA1A inhibits pyroptosis and neuroinflammation after spinal cord injury via DUSP1 inhibition of the MAPK signaling pathway.

He X, Deng B, Zhang C, Zhang G, Yang F, Zhu D Mol Med. 2025; 31(1):53.

PMID: 39924492 PMC: 11809008. DOI: 10.1186/s10020-025-01086-9.

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