Necroptosis信号通路与靶向治疗的研究进展

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。

Recent advances in signal pathway of necroptosis and necroptosis targeted therapies

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.