The Hatter Cardiovascular Institute, University College London Hospital and Medical School, London, UK.
J Cell Mol Med. 2011 Sep;15(9):1797-806. doi: 10.1111/j.1582-4934.2011.01341.x.
Cell death is an integral part of the life of an organism being necessary for the maintenance of organs and tissues. If, however, cell death is allowed to proceed unrestricted, tissue damage and degenerative disease may ensue. Until recently, three morphologically distinct types of cell death were recognized, apoptosis (type I), autophagy (type II) and necrosis (type III). Apoptosis is a highly regulated, genetically determined mechanism designed to dismantle cells systematically (e.g. cells that are no longer functionally viable), via protease (caspase) action, and maintain homeostasis. Autophagy is responsible for the degradation of cytoplasmic material, e.g. proteins and organelles, through autophagosome formation and subsequent proteolytic degradation by lysosomes, and is normally considered in the context of survival although it is sometimes associated with cell death. Necrosis was formerly considered to be an accidental, unregulated form of cell death resulting from excessive stress, although it has been suggested that this is an over-simplistic view as necrosis may under certain circumstances involve the mobilization of specific transduction mechanisms. Indeed, recently, an alternative death pathway, termed necroptosis, was delineated and proposed as a form of 'programmed necrosis'. Identified with the aid of specific inhibitors called necrostatins, necroptosis shares characteristics with both necrosis and apoptosis. Necroptosis involves Fas/tumour necrosis factor-α death domain receptor activation and inhibition of receptor-interacting protein I kinase, and it has been suggested that it may contribute to the development of neurological and myocardial diseases. Significantly, necrostatin-like drugs have been mooted as possible future therapeutic agents for the treatment of degenerative conditions.
细胞死亡是生物生命的一个组成部分，对于维持器官和组织的正常功能是必要的。然而，如果细胞死亡不受限制地进行，可能会导致组织损伤和退行性疾病。直到最近，人们才认识到三种形态上明显不同的细胞死亡类型，即凋亡（I 型）、自噬（II 型）和坏死（III 型）。凋亡是一种高度受调控的、基因决定的机制，通过蛋白酶（半胱天冬酶）的作用，系统地拆除细胞（例如不再具有功能的细胞），以维持体内平衡。自噬负责降解细胞质物质，如蛋白质和细胞器，通过自噬体的形成和随后溶酶体的蛋白水解降解，虽然通常被认为是在生存的背景下，但有时也与细胞死亡有关。坏死以前被认为是一种意外的、不受调节的细胞死亡形式，是由于过度应激引起的，尽管有人认为这种观点过于简单化，因为在某些情况下，坏死可能涉及特定转导机制的动员。事实上，最近，一种被称为坏死性凋亡的替代死亡途径被描述为一种“程序性坏死”形式。在特定抑制剂（称为坏死抑制剂）的帮助下被识别，坏死性凋亡与坏死和凋亡都有共同的特征。坏死性凋亡涉及 Fas/肿瘤坏死因子-α死亡结构域受体的激活和受体相互作用蛋白激酶 I 的抑制，有人认为它可能导致神经和心肌疾病的发展。值得注意的是，类似坏死抑制剂的药物被认为是治疗退行性疾病的潜在未来治疗剂。
