Shao Hongming, Wu Wenbin, Wang Pei, Han Ting, Zhuang Chunlin
School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China.
ACS Chem Neurosci. 2022 Dec 7;13(23):3213-3229. doi: 10.1021/acschemneuro.2c00405. Epub 2022 Nov 14.
Necroptosis is a type of precisely regulated necrotic cell death activated in caspase-deficient conditions. Multiple factors initiate the necroptotic signaling pathway, including toll-like receptor 3/4, tumor necrosis factor (TNF), dsRNA viruses, and T cell receptors. Presently, TNF-induced necroptosis via the phosphorylation of three key proteins, receptor-interacting protein kinase 1, receptor-interacting protein kinase 3, and mixed lineage kinase domain-like protein, is the best-characterized process. Necroptosis induced by Z-DNA-binding protein 1 (ZBP-1) and toll/interleukin-1 receptor (TIR)-domain-containing adapter-inducing interferon (TRIF) plays a significant role in infectious diseases, such as influenza A virus, Zika virus, and herpesvirus infection. An increasing number of studies have demonstrated the close association of necroptosis with multiple diseases, and disrupting necroptosis has been confirmed to be effective for treating (or managing) these diseases. The central nervous system (CNS) exhibits unique physiological structures and immune characteristics. Necroptosis may occur without the sequential activation of signal proteins, and the necroptosis of supporting cells has more important implications in disease development. Additionally, necroptotic signals can be activated in the absence of necroptosis. Here, we summarize the role of necroptosis and its signal proteins in CNS diseases and characterize typical necroptosis regulators to provide a basis for the further development of therapeutic strategies for treating such diseases. In the present review, relevant information has been consolidated from recent studies (from 2010 until the present), excluding the patents in this field.
坏死性凋亡是一种在半胱天冬酶缺陷条件下激活的精确调控的坏死性细胞死亡。多种因素可启动坏死性凋亡信号通路，包括Toll样受体3/4、肿瘤坏死因子（TNF）、双链RNA病毒和T细胞受体。目前，TNF通过三种关键蛋白（受体相互作用蛋白激酶1、受体相互作用蛋白激酶3和混合谱系激酶结构域样蛋白）的磷酸化诱导坏死性凋亡，是最具特征的过程。由Z-DNA结合蛋白1（ZBP-1）和含Toll/白细胞介素-1受体（TIR）结构域的衔接蛋白诱导干扰素（TRIF）诱导的坏死性凋亡在甲型流感病毒、寨卡病毒和疱疹病毒感染等传染病中起重要作用。越来越多的研究表明坏死性凋亡与多种疾病密切相关，并且破坏坏死性凋亡已被证实对治疗（或管理）这些疾病有效。中枢神经系统（CNS）具有独特的生理结构和免疫特征。坏死性凋亡可能在信号蛋白未顺序激活的情况下发生，并且支持细胞的坏死性凋亡在疾病发展中具有更重要的意义。此外，坏死性凋亡信号可在无坏死性凋亡的情况下被激活。在此，我们总结坏死性凋亡及其信号蛋白在中枢神经系统疾病中的作用，并对典型的坏死性凋亡调节因子进行表征，为进一步开发治疗此类疾病的策略提供依据。在本综述中，相关信息整合自最近的研究（从2010年至今），不包括该领域的专利。
