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Role of pyroptosis in spinal cord injury and its therapeutic implications
Abdullah Al Mamun1, Yanqing Wu2, Ilma Monalisa3
1Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035 Zhejiang Province, China.
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.
Insights
Pyroptosis, a programmed cell death, contributes to spinal cord injury (SCI) pathogenesis by releasing inflammatory factors. Inhibiting pyroptosis signaling pathways offers a promising therapeutic strategy for SCI treatment.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Spinal cord injury (SCI) causes neuropathological conditions and neuronal damage.
- Pyroptosis is a programmed cell death pathway involving caspase activation and inflammatory responses.
Purpose of the Study:
- To review the role of pyroptosis in SCI pathogenesis.
- To highlight therapeutic strategies targeting pyroptosis signaling pathways for SCI treatment.
Main Methods:
- Literature review of molecular and pathophysiological mechanisms of pyroptosis in SCI.
- Analysis of pyroptosis signaling pathways and inflammasome components.
Main Results:
- Pyroptosis involves cell swelling, membrane lysis, and release of inflammatory cytokines like IL-18 and IL-1β.
- Gasdermin D (GSDMD) mediates pyroptosis by forming pores in the plasma membrane.
- Pyroptosis plays a critical role in the pathogenesis of SCI and other neurological disorders.
Conclusions:
- Targeting pyroptosis and inflammasome components presents a potential therapeutic avenue for SCI.
- Inhibiting pyroptosis-regulated cell death could be a future treatment for spinal cord injuries.
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