Different Ways to Die: Cell Death Pathways and Their Association With Spinal Cord Injury

Abstract

Cell death is a systematic/nonsystematic process of cessation of normal morphology and functional properties of the cell to replace and recycle old cells with new also promoting inflammation in some cases. It is a complicated process comprising multiple pathways. Some are well-explored, and others have just begun to be. The research on appropriate control of cell death pathways after acute and chronic damage of neuronal cells is being widely researched today due to the lack of regeneration and recovering potential of a neuronal cell after sustaining damage and the inability to control the direction of neuronal growth. In the progression and onset of various neurological diseases, impairments in programmed cell death signaling processes, like necroptosis, apoptosis, ferroptosis, pyroptosis, and pathways directly or indirectly linked, like autophagy as in nonprogrammed necrosis, are observed. Spinal cord injury (SCI) involves the temporary or permanent disruption of motor activities due to the death of a neuronal and glial cell in the spinal cord accompanied by axonal degeneration. Recent years have seen a significant increase in research on the intricate biochemical interactions that occur after a SCI. Different cell death pathways may significantly impact the subsequent damage processes that lead to the eventual neurological deficiency after an injury to the spinal cord. A better knowledge of the molecular basis of the involved cell death pathways might help enhance neuronal and glial survival and neurological deficits, promoting a curative path for SCI.

The role of apoptosis in spinal cord injury: a bibliometric analysis from 1994 to 2023

“…Extensive inflammatory responses after SCI may result in elevated release of pro-inflammatory cytokines and neuronal apoptosis. Inhibiting neuronal apoptosis is conducive to the motor functional recovery post SCI ( Guha et al, 2023 ). Neuronal apoptosis is identified in 4 h after SCI and reaches the peak 8 h later.…”

Commentary on “Different Ways to Die: Cell Death Pathways and Their Association With Spinal Cord Injury”

“…(A) SCI can induce substantial neuronal death, which inhibits neurogenesis and functional recovery. (B) A variety of cell death pathways have been identified in Guha et al recent review paper [ 7 ], each with associated cell signaling pathways and defined cellular events. (C) This publication is well suited to inform subsequent work aimed at developing new therapeutics for SCI, including but not limited to bioinformatics, apoptosis/nonapoptosis checkpoint inhibitors, and drug development for enhanced specificity and reduced side effects.…”

“…In the June 2023 issue of Neurospine , Guha et al [ 7 ] have compiled the most pertinent literature on cell death mechanisms in SCI. In this manuscript, the authors investigated the key cellular pathways related to SCI pathogenesis, the key signaling proteins involved, and the current treatment options ( Fig.…”

“…Here, readers are encouraged to use this manuscript as a stepping stone toward the next step in targeted SCI treatment research and development. For example, the systematic review of key cellular death pathways laid in the manuscript of Guha et al [ 7 ] can be readily integrated into a variety of studies. Mechanistic investigations into novel SCI treatment options, such as systemic hypothermia, can be accelerated with the manuscript of Guha et al [ 6 , 7 ].…”

ROS-responsive nanoparticle delivery of ferroptosis inhibitor prodrug to facilitate mesenchymal stem cell-mediated spinal cord injury repair

“…When SCI occurs, the overproduction of reactive oxygen species (ROS) leads to depletion of endogenous antioxidants and disruption of redox homeostasis, which can lead to ferroptosis, and exacerbate the inflammatory response [ 24 , 25 ]. Emerging evidence indicates that ferroptosis is a distinct form of oxidative cell death that plays an essential role in pathogenesis in SCI [ 26 , 27 ].…”