Department for Molecular Biomedical Research, VIB, Ghent University, Belgium.
Nat Rev Mol Cell Biol. 2010 Oct;11(10):700-14. doi: 10.1038/nrm2970. Epub 2010 Sep 8.
For a long time, apoptosis was considered the sole form of programmed cell death during development, homeostasis and disease, whereas necrosis was regarded as an unregulated and uncontrollable process. Evidence now reveals that necrosis can also occur in a regulated manner. The initiation of programmed necrosis, 'necroptosis', by death receptors (such as tumour necrosis factor receptor 1) requires the kinase activity of receptor-interacting protein 1 (RIP1; also known as RIPK1) and RIP3 (also known as RIPK3), and its execution involves the active disintegration of mitochondrial, lysosomal and plasma membranes. Necroptosis participates in the pathogenesis of diseases, including ischaemic injury, neurodegeneration and viral infection, thereby representing an attractive target for the avoidance of unwarranted cell death.
长期以来，细胞凋亡被认为是发育、内稳态和疾病过程中细胞程序性死亡的唯一形式，而坏死则被认为是一种不受调节和不可控制的过程。现在有证据表明，坏死也可以以受调控的方式发生。由死亡受体（如肿瘤坏死因子受体 1）启动的程序性细胞坏死，即“坏死性凋亡”，需要受体相互作用蛋白 1（RIP1；也称为 RIPK1）和 RIP3（也称为 RIPK3）的激酶活性，其执行涉及线粒体、溶酶体和质膜的主动解体。坏死性凋亡参与了包括缺血性损伤、神经退行性变和病毒感染在内的多种疾病的发病机制，因此成为避免不必要的细胞死亡的一个有吸引力的治疗靶点。
