Necroptosis refers to a regulated form of cell death induced by a variety of stimuli. Although it has been implicated in the pathogenesis of many diseases, there is evidence to support that necroptosis is not purely a detrimental process. We propose that necroptosis is a “double-edged sword” in terms of physiology and pathology. On the one hand, necroptosis can trigger an uncontrolled inflammatory cascade response, resulting in severe tissue injury, disease chronicity, and even tumor progression. On the other hand, necroptosis functions as a host defense mechanism, exerting antipathogenic and antitumor effects through its powerful pro-inflammatory properties. Moreover, necroptosis plays an important role during both development and regeneration. Misestimation of the multifaceted features of necroptosis may influence the development of therapeutic approaches targeting necroptosis. In this review, we summarize current knowledge of the pathways involved in necroptosis as well as five important steps that determine its occurrence. The dual role of necroptosis in a variety of physiological and pathological conditions is also highlighted. Future studies and the development of therapeutic strategies targeting necroptosis should fully consider the complicated properties of this type of regulated cell death.

坏死性凋亡是指由各种刺激诱导的细胞死亡的调节形式。尽管它与许多疾病的发病机制有关，但有证据表明坏死性凋亡不仅仅是一个有害过程。我们认为坏死性凋亡在生理学和病理学方面是一把“双刃剑”。一方面，坏死性凋亡可引发不受控制的炎症级联反应，导致严重的组织损伤、疾病慢性化甚至肿瘤进展。另一方面，坏死性凋亡作为宿主防御机制发挥作用，通过其强大的促炎特性发挥抗病原体和抗肿瘤作用。此外，坏死性凋亡在发育和再生过程中起着重要作用。对坏死性凋亡多方面特征的错误估计可能会影响针对坏死性凋亡的治疗方法的发展。在这篇综述中，我们总结了当前关于坏死性凋亡相关通路的知识以及决定其发生的五个重要步骤。还强调了坏死性凋亡在各种生理和病理条件下的双重作用。未来的研究和针对坏死性凋亡的治疗策略的开发应充分考虑这种类型的受调节细胞死亡的复杂特性。