Journal of Advanced Research ( IF 11.4 ) Pub Date : 2020-08-18 , DOI: 10.1016/j.jare.2020.08.004 Abdullah Al Mamun 1 , Yanqing Wu 2 , Ilma Monalisa 3 , Chang Jia 4 , Kailiang Zhou 5 , Fahad Munir 6 , Jian Xiao 1
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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.
中文翻译：
焦亡在脊髓损伤中的作用及其治疗意义
背景
目前，脊髓损伤（SCI）是一种病理事件，会引发多种神经病理状况，导致神经元损伤并释放多种促炎介质。然而，焦亡被认为是一种新的程序性细胞死亡机制，通过刺激 caspase-1 和/或 caspase-11/-4/-5 信号通路以及一系列炎症反应来调节。
目的
我们目前的综述根据几种分子和病理生理学机制，简要总结了焦亡调节的程序性细胞死亡在 SCI 中的潜在作用。本综述还强调了焦亡信号通路和炎症小体成分的靶向及其对 SCI 治疗的治疗意义。
关键科学概念
多项证据表明焦亡在细胞肿胀、质膜溶解、染色质断裂和细胞内促炎因子（包括 IL-18 和 IL-1β 释放）中发挥着重要作用。此外，焦亡是由最近发现的称为 GSDMD 的成孔蛋白家族直接介导的。目前的研究表明，细胞焦亡调节的细胞死亡在多种神经系统疾病以及 SCI 的发病机制中发挥着关键作用。我们的叙述性文章表明，抑制焦亡调节的细胞死亡和炎症小体成分可能是在不久的将来治疗 SCI 的一种有前途的治疗方法。
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