Purpose of review

Necroptosis is a form of cell death regulated by specific cellular protein machinery. Although the cell death is tightly controlled like apoptosis, another type of programed cell death, the biological features of necroptosis rather resemble necrosis that is defined as an uncontrolled accidental cell death. The pathway executing necroptosis relies on a protein kinase, RIPK3, and its downstream effector molecule, MLKL. Upon necroptosis initiating signals, both RIPK3 and MLKL undergo extensive post-translation modifications to construct a death complex called necrosome, finally leading to lysis of cell membrane. Preclinical mouse models demonstrated the physiological importance of necroptosis in the progress of various inflammation-associated diseases. The objective of this brief review is to introduce a new emerging concept in cell death biology and to provide a first entry into the research field of necroptosis.

Recent findings

The uncovering of necroptosis pathway brought a fundamental change in the basic concept that necrotic cell death is passive and unregulated. Currently, multiple small molecules that can target necrotic cell death are under development and some of them are under clinical trials to evaluate their therapeutic potentials. Better understanding of the molecular mechanism leveraging necroptosis will provide an unprecedented opportunity to pathological necrosis-driven human diseases.

中文翻译：

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坏死病的调制及其治疗潜力

审查目的

坏死病是细胞死亡的一种形式，受特定细胞蛋白机制调控。尽管像细胞凋亡（细胞凋亡的另一种类型的程序性死亡）一样，细胞死亡受到严格控制，但尸体坏死的生物学特征与坏死很像，坏死被定义为不受控制的意外细胞死亡。执行坏死病的途径依赖于蛋白激酶RIPK3及其下游效应分子MLKL。坏死启动信号发出后，RIPK3和MLKL均进行广泛的翻译后修饰，以构建称为坏死体的死亡复合体，最终导致细胞膜溶解。临床前小鼠模型证明了坏死病在各种炎症相关疾病进展中的生理重要性。

最近的发现

坏死病途径的发现使坏死细胞死亡是被动的且不受调节的基本概念发生了根本变化。目前，正在开发能够靶向坏死细胞死亡的多种小分子，其中一些正在进行临床试验以评估其治疗潜力。更好地了解利用坏死性坏死的分子机制将为病理性坏死驱动的人类疾病提供前所未有的机会。