Necroptosis is a regulated cell death pathway morphologically similar to necrosis that depends on the kinase activity of receptor interacting protein 3 (RIP3) and the subsequent activation of the pseudokinase mixed lineage kinase domain-like protein (MLKL), being also generally dependent on RIP1 kinase activity. Necroptosis can be recruited during pathological conditions, usually following the activation of death receptors under specific cellular contexts. In this regard, necroptosis has been implicated in the pathogenesis of multiple disorders, including acute and chronic neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases, and multiple sclerosis. Here, we summarize the molecular mechanisms regulating the induction of necroptosis and downstream effectors of this form of cell death, besides exploring non-necroptotic roles for necroptosis-related proteins that may impact on alternative cell death pathways and inflammatory mechanisms in disease. Finally, we outline the recent evidence implicating necroptosis in neurodegenerative conditions and the emerging therapeutic perspectives targeting necroptosis in these diseases.

中文翻译：

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坏死的分子机制及其与神经退行性疾病的相关性。

坏死性坏死是一种受调节的细胞死亡途径，在形态上类似于坏死，这取决于受体相互作用蛋白3（RIP3）的激酶活性以及随后的伪激酶混合谱系激酶结构域样蛋白（MLKL）的激活，而后者通常也依赖于RIP1激酶活动。可以在病理条件下募集坏死病，通常是在特定细胞环境下激活死亡受体之后。在这方面，坏死病涉及多种疾病的发病机理，包括急性和慢性神经退行性疾病，例如帕金森氏病和阿尔茨海默氏病，以及多发性硬化症。在这里，我们总结了调节这种形式细胞死亡的坏死性坏死和下游效应子诱导的分子机制，除了探讨坏死相关蛋白的非坏死作用外，还可能影响疾病的其他细胞死亡途径和炎症机制。最后，我们概述了神经退行性疾病中坏死性坏死的最新证据以及针对这些疾病中坏死性坏死的新兴治疗方法。