Microglial pyroptosis as a therapeutic target after traumatic spinal cord injury: current progress and future directions
Traumatic spinal cord injury (TSCI) is a devastating neurological condition with limited therapeutic options and a high likelihood of permanent disability. Among the multifaceted secondary injury mechanisms triggered by TSCI, pyroptosis—an inflammatory form of programmed cell death—has emerged as a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1649790/full |
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| author | Lei Shi Lei Shi Lei Shi Qiheng Qian Jiding Xie Taoshuo Yang Xinyu Zhao Xiangqi Meng Jingang Dai Qiguan Jin |
| author_facet | Lei Shi Lei Shi Lei Shi Qiheng Qian Jiding Xie Taoshuo Yang Xinyu Zhao Xiangqi Meng Jingang Dai Qiguan Jin |
| author_sort | Lei Shi |
| collection | DOAJ |
| description | Traumatic spinal cord injury (TSCI) is a devastating neurological condition with limited therapeutic options and a high likelihood of permanent disability. Among the multifaceted secondary injury mechanisms triggered by TSCI, pyroptosis—an inflammatory form of programmed cell death—has emerged as a key pathological process. In particular, microglial pyroptosis plays a pivotal role in exacerbating neuroinflammation and disrupting tissue homeostasis, thereby amplifying the secondary injury cascade. This review provides a comprehensive overview of the molecular pathways mediating microglial pyroptosis, including canonical (NLRP3–caspase-1–GSDMD), non-canonical (caspase-11–GSDMD), and atypical (caspase-3/8–GSDME/GSDMC) signaling. We also examine recent therapeutic strategies aimed at suppressing microglial pyroptosis—such as extracellular vesicle-based delivery systems, small-molecule compounds, and gene-targeted approaches—and assess their potential to enhance neurological and motor recovery following SCI. By elucidating both the pathological significance and therapeutic promise of microglial pyroptosis, this review offers novel perspectives on its translational potential as a target for spinal cord injury intervention. |
| format | Article |
| id | doaj-art-242062957ead444ead63daa9ddeb2f6d |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-242062957ead444ead63daa9ddeb2f6d2025-08-22T04:10:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16497901649790Microglial pyroptosis as a therapeutic target after traumatic spinal cord injury: current progress and future directionsLei Shi0Lei Shi1Lei Shi2Qiheng Qian3Jiding Xie4Taoshuo Yang5Xinyu Zhao6Xiangqi Meng7Jingang Dai8Qiguan Jin9College of Physical Education, Yangzhou University, Yangzhou, Jiangsu, ChinaSuzhou Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu, ChinaExperimental Research Center, China Academy of Chinese Medical Sciences, Beijing, ChinaSuzhou Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu, ChinaExperimental Research Center, China Academy of Chinese Medical Sciences, Beijing, ChinaCollege of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United KingdomXuzhou Hospital of Traditional Chinese Medicine, Xuzhou, Jiangsu, ChinaSuzhou Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu, ChinaExperimental Research Center, China Academy of Chinese Medical Sciences, Beijing, ChinaCollege of Physical Education, Yangzhou University, Yangzhou, Jiangsu, ChinaTraumatic spinal cord injury (TSCI) is a devastating neurological condition with limited therapeutic options and a high likelihood of permanent disability. Among the multifaceted secondary injury mechanisms triggered by TSCI, pyroptosis—an inflammatory form of programmed cell death—has emerged as a key pathological process. In particular, microglial pyroptosis plays a pivotal role in exacerbating neuroinflammation and disrupting tissue homeostasis, thereby amplifying the secondary injury cascade. This review provides a comprehensive overview of the molecular pathways mediating microglial pyroptosis, including canonical (NLRP3–caspase-1–GSDMD), non-canonical (caspase-11–GSDMD), and atypical (caspase-3/8–GSDME/GSDMC) signaling. We also examine recent therapeutic strategies aimed at suppressing microglial pyroptosis—such as extracellular vesicle-based delivery systems, small-molecule compounds, and gene-targeted approaches—and assess their potential to enhance neurological and motor recovery following SCI. By elucidating both the pathological significance and therapeutic promise of microglial pyroptosis, this review offers novel perspectives on its translational potential as a target for spinal cord injury intervention.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1649790/fulltraumatic spinal cord injurypyroptosismicrogliainflammationNLRP3GSDMD |
| spellingShingle | Lei Shi Lei Shi Lei Shi Qiheng Qian Jiding Xie Taoshuo Yang Xinyu Zhao Xiangqi Meng Jingang Dai Qiguan Jin Microglial pyroptosis as a therapeutic target after traumatic spinal cord injury: current progress and future directions Frontiers in Immunology traumatic spinal cord injury pyroptosis microglia inflammation NLRP3 GSDMD |
| title | Microglial pyroptosis as a therapeutic target after traumatic spinal cord injury: current progress and future directions |
| title_full | Microglial pyroptosis as a therapeutic target after traumatic spinal cord injury: current progress and future directions |
| title_fullStr | Microglial pyroptosis as a therapeutic target after traumatic spinal cord injury: current progress and future directions |
| title_full_unstemmed | Microglial pyroptosis as a therapeutic target after traumatic spinal cord injury: current progress and future directions |
| title_short | Microglial pyroptosis as a therapeutic target after traumatic spinal cord injury: current progress and future directions |
| title_sort | microglial pyroptosis as a therapeutic target after traumatic spinal cord injury current progress and future directions |
| topic | traumatic spinal cord injury pyroptosis microglia inflammation NLRP3 GSDMD |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1649790/full |
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