Programmed Cell Death in Spinal Cord Injury Pathogenesis and Therapy

Overview

Journal Cell Prolif

Date 2021 Jan 28

PMID 33506613

Citations 100

Authors

Zhongju Shi

Shiyang Yuan

Linlin Shi

Jiahe Li

Guangzhi Ning

Xiaohong Kong

Shiqing Feng

Affiliations

Soon will be listed here.

Abstract

Spinal cord injury (SCI) always leads to functional deterioration due to a series of processes including cell death. In recent years, programmed cell death (PCD) is considered to be a critical process after SCI, and various forms of PCD were discovered in recent years, including apoptosis, necroptosis, autophagy, ferroptosis, pyroptosis and paraptosis. Unlike necrosis, PCD is known as an active cell death mediated by a cascade of gene expression events, and it is crucial for elimination unnecessary and damaged cells, as well as a defence mechanism. Therefore, it would be meaningful to characterize the roles of PCD to not only enhance our understanding of the pathophysiological processes, but also improve functional recovery after SCI. This review will summarize and explore the most recent advances on how apoptosis, necroptosis, autophagy, ferroptosis, pyroptosis and paraptosis are involved in SCI. This review can help us to understand the various functions of PCD in the pathological processes of SCI, and contribute to our novel understanding of SCI of unknown aetiology in the near future.

Citing Articles

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.

50 years of methylprednisolone application in spinal cord injury: a bibliometric analysis.

Zhou M, Xu Z, Feng L, Zhong H, Yang H, Ning G Acta Neurochir (Wien). 2025; 167(1):38.

PMID: 39915313 PMC: 11802693. DOI: 10.1007/s00701-025-06443-5.

TRIM32 promotes neuronal ferroptosis by enhancing K63-linked ubiquitination and subsequent p62-selective autophagic degradation of GPX4.

Zhou X, Zhao Y, Huang S, Shu H, Zhang Y, Yang H Int J Biol Sci. 2025; 21(3):1259-1274.

PMID: 39897031 PMC: 11781169. DOI: 10.7150/ijbs.106690.

Inhibition of CD36 ameliorates mouse spinal cord injury by accelerating microglial lipophagy.

Wang B, Du A, Chen X, Huang T, Al Mamun A, Li P Acta Pharmacol Sin. 2025; .

PMID: 39880928 DOI: 10.1038/s41401-024-01463-w.

Glycosylated lysosomal membrane protein promotes tissue repair after spinal cord injury by reducing iron deposition and ferroptosis in microglia.

Ouyang F, Zheng M, Li J, Huang J, Ye J, Wang J Sci Rep. 2025; 15(1):2867.

PMID: 39843796 PMC: 11754889. DOI: 10.1038/s41598-025-86991-z.

References

Shuman S, Bresnahan J, Beattie M . Apoptosis of microglia and oligodendrocytes after spinal cord contusion in rats. J Neurosci Res. 1998; 50(5):798-808. DOI: 10.1002/(SICI)1097-4547(19971201)50:5<798::AID-JNR16>3.0.CO;2-Y. View

Stockwell B, Friedmann Angeli J, Bayir H, Bush A, Conrad M, Dixon S . Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. Cell. 2017; 171(2):273-285. PMC: 5685180. DOI: 10.1016/j.cell.2017.09.021. View

Li R, Zhang L, Sun W . Erythropoietin rescues primary rat cortical neurons from pyroptosis and apoptosis via Erk1/2-Nrf2/Bach1 signal pathway. Brain Res Bull. 2017; 130:236-244. DOI: 10.1016/j.brainresbull.2017.01.016. View

Yang H, Mei J, Chang K, Zhou W, Huang L, Li M . Autophagy in endometriosis. Am J Transl Res. 2017; 9(11):4707-4725. PMC: 5714760. View

Zhaolin Z, Guohua L, Shiyuan W, Zuo W . Role of pyroptosis in cardiovascular disease. Cell Prolif. 2018; 52(2):e12563. PMC: 6496801. DOI: 10.1111/cpr.12563. View

Sperandio S, de Belle I, Bredesen D . An alternative, nonapoptotic form of programmed cell death. Proc Natl Acad Sci U S A. 2000; 97(26):14376-81. PMC: 18926. DOI: 10.1073/pnas.97.26.14376. View

Chen H, Hsu P, Tzaan W, Lee A . Effects of the combined administration of vitamins C and E on the oxidative stress status and programmed cell death pathways after experimental spinal cord injury. Spinal Cord. 2013; 52(1):24-8. DOI: 10.1038/sc.2013.140. View

Wang Y, Lee C . MicroRNA and cancer--focus on apoptosis. J Cell Mol Med. 2009; 13(1):12-23. PMC: 3823033. DOI: 10.1111/j.1582-4934.2008.00510.x. View

Saunders L, Clarke A, Tate D, Forchheimer M, Krause J . Lifetime prevalence of chronic health conditions among persons with spinal cord injury. Arch Phys Med Rehabil. 2014; 96(4):673-9. DOI: 10.1016/j.apmr.2014.11.019. View

10.

Wang J, Luo X, Liu L . Targeting CARD6 attenuates spinal cord injury (SCI) in mice through inhibiting apoptosis, inflammation and oxidative stress associated ROS production. Aging (Albany NY). 2019; 11(24):12213-12235. PMC: 6949089. DOI: 10.18632/aging.102561. View

11.

Bai L, Mei X, Wang Y, Yuan Y, Bi Y, Li G . The Role of Netrin-1 in Improving Functional Recovery through Autophagy Stimulation Following Spinal Cord Injury in Rats. Front Cell Neurosci. 2017; 11:350. PMC: 5701630. DOI: 10.3389/fncel.2017.00350. View

12.

Emery E, Aldana P, Bunge M, PUCKETT W, Srinivasan A, Keane R . Apoptosis after traumatic human spinal cord injury. J Neurosurg. 1998; 89(6):911-20. DOI: 10.3171/jns.1998.89.6.0911. View

13.

Lu X, Fan Q, Xu L, Li L, Yue Y, Xu Y . Ursolic acid attenuates diabetic mesangial cell injury through the up-regulation of autophagy via miRNA-21/PTEN/Akt/mTOR suppression. PLoS One. 2015; 10(2):e0117400. PMC: 4331365. DOI: 10.1371/journal.pone.0117400. View

14.

Wu C, Chen J, Liu Y, Zhang J, Ding W, Wang S . Upregulation of PSMB4 is Associated with the Necroptosis after Spinal Cord Injury. Neurochem Res. 2016; 41(11):3103-3112. DOI: 10.1007/s11064-016-2033-7. View

15.

Fink S, Cookson B . Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect Immun. 2005; 73(4):1907-16. PMC: 1087413. DOI: 10.1128/IAI.73.4.1907-1916.2005. View

16.

Kim J, Paton J, Briles D, Rhee D, Pyo S . Streptococcus pneumoniae induces pyroptosis through the regulation of autophagy in murine microglia. Oncotarget. 2015; 6(42):44161-78. PMC: 4792549. DOI: 10.18632/oncotarget.6592. View

17.

Green D . Apoptotic pathways: the roads to ruin. Cell. 1998; 94(6):695-8. DOI: 10.1016/s0092-8674(00)81728-6. View

18.

Shi Z, Zhou H, Lu L, Li X, Fu Z, Liu J . The roles of microRNAs in spinal cord injury. Int J Neurosci. 2017; 127(12):1104-1115. DOI: 10.1080/00207454.2017.1323208. View

19.

Kanno H, Ozawa H, Sekiguchi A, Yamaya S, Itoi E . Induction of autophagy and autophagic cell death in damaged neural tissue after acute spinal cord injury in mice. Spine (Phila Pa 1976). 2011; 36(22):E1427-34. DOI: 10.1097/BRS.0b013e3182028c3a. View

20.

Zha J, Smith A, Andreansky S, Bracchi-Ricard V, Bethea J . Chronic thoracic spinal cord injury impairs CD8+ T-cell function by up-regulating programmed cell death-1 expression. J Neuroinflammation. 2014; 11:65. PMC: 4230802. DOI: 10.1186/1742-2094-11-65. View