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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。
Necroptosis is a regulatable, apoptotic pathway that has the same morphological characteristics as non-regulatable necrosis. Necroptosis is caspase-independent. When apoptosis is blocked, the necroptosis signaling pathway is activated by the death domain activation, in which activation of RIP1 is a key step in necroptosis that can be specifically inhibited by necrostatin-1. Recent studies have shown that necroptosis plays an important role in the pathophysiological processes of many diseases such as ischemic injury, neurodegenerative diseases, malignant tumors, viral infections and autoimmune diseases, and is expected to serve as a new target for drug development. This review summarizes the discovery of necroptosis, its signaling pathway and its role in pathophysiological mechanisms and therapies targeting necroptosis.