Zhou Conghui, Zheng Jinfeng, Fan Yunpeng, Wu Junsong
The First Affiliated Hospital of Zhejiang University, School of Medicine, Zhejiang University, Hangzhou, China.
Department of Orthopaedics of the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Front Cell Dev Biol. 2022 Feb 2;10:821225. doi: 10.3389/fcell.2022.821225. eCollection 2022.
Central nervous system (CNS) trauma, including traumatic brain injury (TBI) and traumatic spinal cord injury (SCI), is characterized by high morbidity, disability, and mortality. TBI and SCI have similar pathophysiological mechanisms and are often accompanied by serious inflammatory responses. Pyroptosis, an inflammation-dependent programmed cell death, is becoming a major problem in CNS post-traumatic injury. Notably, the pyrin domain containing 3 (NLRP3) inflammasome is a key protein in the pyroptosis signaling pathway. Therefore, underlying mechanism of the NLRP3 inflammasome in the development of CNS trauma has attracted much attention. In this review, we briefly summarize the molecular mechanisms of NLRP3 inflammasome in pyroptosis signaling pathway, including its prime and activation. Moreover, the dynamic expression pattern, and roles of the NLRP3 inflammasome in CNS post-traumatic injury are summarized. The therapeutic applications of NLRP3 inflammasome activation inhibitors are also discussed.
中枢神经系统（CNS）创伤，包括创伤性脑损伤（TBI）和创伤性脊髓损伤（SCI），具有高发病率、高致残率和高死亡率的特点。TBI和SCI具有相似的病理生理机制，并且常伴有严重的炎症反应。细胞焦亡是一种依赖炎症的程序性细胞死亡，正成为中枢神经系统创伤后损伤的一个主要问题。值得注意的是，含pyrin结构域3（NLRP3）炎性小体是细胞焦亡信号通路中的关键蛋白。因此，NLRP3炎性小体在中枢神经系统创伤发生发展中的潜在机制已引起广泛关注。在本综述中，我们简要总结了NLRP3炎性小体在细胞焦亡信号通路中的分子机制，包括其启动和激活。此外，还总结了NLRP3炎性小体在中枢神经系统创伤后损伤中的动态表达模式及其作用。同时也讨论了NLRP3炎性小体激活抑制剂的治疗应用。
