Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou 325027, China; The Second Clinical Medical College of Wenzhou Medical University, Wenzhou 325027, China.
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou 325027, China; The Second Clinical Medical College of Wenzhou Medical University, Wenzhou 325027, China.
J Adv Res. 2022 Sep;40:125-134. doi: 10.1016/j.jare.2021.12.002. Epub 2021 Dec 22.
Traumatic brain injury (TBI) and spinal cord injury (SCI) are capable of causing severe sensory, motor and autonomic nervous system dysfunctions. However, effective treatments for TBI and SCI are still unavailable, mainly because the death of nerve cells is uncontrollable. Necroptosis is a type of programmed cell death and a critical mechanism in the process of neuronal cell death. However, the role of necroptosis has not been comprehensively defined in TBI and SCI.
This review aimed to summarize the role of necroptosis in central nervous system (CNS) trauma and its therapeutic implications and present important suggestions for researchers conducting in-depth research.
Necroptosis is orchestrated by a complex comprising the receptor-interacting protein kinase (RIPK)1, RIPK3 and mixed lineage kinase domain-like protein (MLKL) proteins. Mechanistically, RIPK1 and RIPK3 form a necrosome with MLKL. After MLKL dissociates from the necrosome, it translocates to the plasma membrane to induce pore formation in the membrane and then induces necroptosis. In this review, the necroptosis signalling pathway and the execution of necroptosis are briefly discussed. In addition, we focus on the existing information on the mechanism by which necroptosis participates in CNS trauma, particularly in the temporal pattern of RIPKs and in different cell types. Furthermore, we describe the association of miRNAs and necroptosis and the relationship between different types of CNS trauma cell death. Finally, this study highlights agents likely capable of curtailing such a type of cell death according to results optimization and CNS trauma and presents important suggestions for researchers conducting in-depth research.
颅脑损伤（TBI）和脊髓损伤（SCI）可导致严重的感觉、运动和自主神经系统功能障碍。然而，TBI 和 SCI 仍然没有有效的治疗方法，主要是因为神经细胞的死亡是不可控的。细胞坏死是一种程序性细胞死亡，是神经元细胞死亡过程中的一个关键机制。然而，细胞坏死在 TBI 和 SCI 中的作用尚未得到全面定义。
本综述旨在总结细胞坏死在中枢神经系统（CNS）创伤中的作用及其治疗意义，并为深入研究的研究人员提供重要建议。
细胞坏死由包含受体相互作用蛋白激酶（RIPK）1、RIPK3 和混合谱系激酶结构域样蛋白（MLKL）蛋白的复杂机制调控。从机制上讲，RIPK1 和 RIPK3 与 MLKL 形成坏死小体。MLKL 从坏死小体中解离出来后，转移到质膜上，在质膜上诱导孔形成，然后诱导细胞坏死。在本综述中，简要讨论了细胞坏死信号通路和细胞坏死的执行。此外，我们重点介绍了细胞坏死参与 CNS 创伤的现有信息，特别是在 RIPKs 的时间模式和不同细胞类型中的作用。此外，还描述了 miRNA 和细胞坏死之间的关联以及不同类型的 CNS 创伤细胞死亡之间的关系。最后，根据结果优化和 CNS 创伤，本研究强调了可能能够遏制这种类型细胞死亡的药物，并为深入研究的研究人员提供了重要建议。
