Necroptosis信号通路与靶向治疗的研究进展
陈 牧,黄 雷*
(上海交通大学医学院,上海200025)

摘 要:摘 要:Necroptosis 是一种可调控的细胞程序性坏死途径,它具有与不可调控性细胞坏死相同的形态学特征。Necroptosis 是caspase 非依赖的。当细胞凋亡被阻断时,necroptosis 信号通路由死亡结构域激活启动,其中RIP1 的活化是necroptosis 的关键步骤,该步骤可被necrostatin-1 特异性抑制。近期研究表明,necroptosis 在缺血性损伤、神经退行性疾病、恶性肿瘤、病毒感染和免疫性疾病等多种疾病的病理生理过程中起重要作用,有望作为药物开发的新靶点。对necroptosis 的发现历程、信号通路及其在疾病病理生理机制中的作用和靶向necroptosis 的治疗等四个方面进行综述。
关键词:necroptosis ;信号通路;病理生理机制;靶向治疗

Recent advances in signal pathway of necroptosis and necroptosis targeted therapies
CHEN Mu, HUANG Lei*
(School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China)

Abstract: Abstract: Necroptosis is a specialized pathway of programmed necrosis induced by the activation of death domain (DD) under conditions when apoptosis execution is prevented. Necroptosis is caspase-independent, mediated by receptor-interacting protein 1 (RIP1) activity and inhibited by necrostatin-1 (Nec-1). Although it occurs under regulated conditions, necroptosis is characterized by the same morphological features as unregulated necrosis. In recent years, necroptosis has been found playing a significant role in multiple pathophysiologic processes. Targeting necroptosis pathway provides a new strategy for treatment of multiple human diseases involving ischemic injury, neurodegeneration disease, malignant tumor, virus infection and autoimmune disease. This review includes four parts: the discovery of necroptosis; the mechanism and signal pathway of necroptosis; the role that necroptosis plays in pathophysiologic processes of several diseases; the necroptosis targeted therapies.
Key words: necroptosis; signal pathway; pathophysiologic mechanism; targeted therapy

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