Department of Biochemistry, Faculty of Medicine, Toho University School of Medicine, Tokyo, Japan.
Adv Exp Med Biol. 2024;1444:129-143. doi: 10.1007/978-981-99-9781-7_9.
Necroptosis is a regulated form of cell death involved in the development of various pathological conditions. In contrast to apoptosis, plasma membrane rupture (PMR) occurs in cells in the relatively early stage of necroptosis; therefore, necroptosis induces a strong inflammatory response. Stimuli, including tumor necrosis factor (TNF), interferon (IFN)α/β, lipopolysaccharide, polyI:C, and viral infection, induce the formation of necrosomes that lead to membrane rupture and the release of intracellular contents, termed danger-associated molecular patterns (DAMPs). DAMPs are the collective term for molecules that normally reside in the cytoplasm or nucleus in living cells without inducing inflammation but induce strong inflammatory responses when released outside cells. Recent studies have provided a better understanding of the mechanisms underlying PMR and the release of DAMPs. Moreover, necroptosis is involved in various pathological conditions, and mutations in necroptosis-related genes can cause hereditary autoinflammatory syndromes. Thus, manipulating necroptosis signaling pathways may be useful for treating diseases involving necroptosis.
细胞坏死是一种受调控的细胞死亡形式，参与多种病理状况的发生。与细胞凋亡不同，在细胞坏死的相对早期阶段就会发生质膜破裂（PMR）；因此，细胞坏死会引发强烈的炎症反应。肿瘤坏死因子（TNF）、干扰素（IFN）α/β、脂多糖、polyI:C 和病毒感染等刺激因素会诱导形成导致膜破裂和细胞内内容物释放的坏死小体，这些内容物被称为损伤相关分子模式（DAMPs）。DAMPs 是一个术语，用于描述正常情况下存在于活细胞的细胞质或核内而不引发炎症的分子，但当它们被释放到细胞外时，会引发强烈的炎症反应。最近的研究提供了对 PMR 和 DAMPs 释放机制的更好理解。此外，细胞坏死参与多种病理状况，并且与细胞坏死相关的基因突变可导致遗传性自身炎症综合征。因此，操纵细胞坏死信号通路可能有助于治疗涉及细胞坏死的疾病。
