ZBP1-Mediated Necroptosis: Mechanisms and Therapeutic Implications.

ZBP1-Mediated Necroptosis: Mechanisms and Therapeutic Implications.
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DOI:
10.3390/molecules28010052
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发表时间:
2022-12-21
期刊:
Molecules (Basel, Switzerland)
影响因子:
--
通讯作者:
Xiong K
Xiong K
中科院分区:
其他
文献类型:
--
作者:
Chen XY;Dai YH;Wan XX;Hu XM;Zhao WJ;Ban XX;Wan H;Huang K;Zhang Q;Xiong K

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细胞死亡是人类疾病的基本病理生理过程。坏死性凋亡是一种由死亡受体激活和坏死体形成诱导的调节性坏死形式,其发现代表了过去十年细胞死亡领域的重大突破。 Z-DNA 结合蛋白 (ZBP1) 是一种干扰素 (IFN) 诱导蛋白,最初报道为双链 DNA (dsDNA) 传感器,可诱导先天炎症反应。最近,ZBP1被确定为病毒感染过程中坏死性凋亡的重要传感器。它通过两个结构域连接病毒核酸和受体相互作用蛋白激酶 3 (RIPK3),并诱导坏死体的形成。最近的研究还报道,ZBP1在非病毒感染中诱导坏死性凋亡,并通过独特的机制介导坏死信号转导。这篇综述重点介绍了 ZBP1 的发现及其在坏死性凋亡中的新发现,并深入了解了其在不同类型细胞死亡之间串扰中的关键作用,这可能代表了一种新的治疗选择。
Cell death is a fundamental pathophysiological process in human disease. The discovery of necroptosis, a form of regulated necrosis that is induced by the activation of death receptors and formation of necrosome, represents a major breakthrough in the field of cell death in the past decade. Z-DNA-binding protein (ZBP1) is an interferon (IFN)-inducing protein, initially reported as a double-stranded DNA (dsDNA) sensor, which induces an innate inflammatory response. Recently, ZBP1 was identified as an important sensor of necroptosis during virus infection. It connects viral nucleic acid and receptor-interacting protein kinase 3 (RIPK3) via two domains and induces the formation of a necrosome. Recent studies have also reported that ZBP1 induces necroptosis in non-viral infections and mediates necrotic signal transduction by a unique mechanism. This review highlights the discovery of ZBP1 and its novel findings in necroptosis and provides an insight into its critical role in the crosstalk between different types of cell death, which may represent a new therapeutic option.
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