Kers Jesper, Leemans Jaklien C, Linkermann Andreas
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Semin Nephrol. 2016 May;36(3):139-52. doi: 10.1016/j.semnephrol.2016.03.002.
Necrosis is the predominant form of regulated cell death in acute kidney injury (AKI) and represents results in the formation of casts that appear in the urine sedimentation, referred to as muddy brown casts, which are part of the diagnosis of AKI. Pathologists referred to this typical feature as acute tubular necrosis. We are only beginning to understand the dynamics and the molecular pathways that underlie such typical necrotic morphology. In this review, we provide an overview of candidate pathways and summarize the emerging evidence for the relative contribution of these pathways of regulated necrosis, such as necroptosis, ferroptosis, mitochondrial permeability transition-mediated regulated necrosis, parthanatos, and pyroptosis. Inhibitors of each of these pathways are available, and clinical trials may be started after the detection of the most promising drug targets, which will be discussed here. With the global burden of AKI in mind, inhibitiors of regulated necrosis represent promising means to prevent this disease.
坏死是急性肾损伤（AKI）中程序性细胞死亡的主要形式，其结果是形成在尿沉渣中出现的管型，称为泥褐色管型，这是AKI诊断的一部分。病理学家将这种典型特征称为急性肾小管坏死。我们才刚刚开始了解这种典型坏死形态背后的动态过程和分子途径。在这篇综述中，我们概述了候选途径，并总结了这些程序性坏死途径（如坏死性凋亡、铁死亡、线粒体通透性转换介导的程序性坏死、PARP-1依赖性坏死和焦亡）相对贡献的新证据。这些途径的抑制剂均已存在，在检测到最有前景的药物靶点后可能会启动临床试验，本文将对此进行讨论。考虑到全球AKI的负担，程序性坏死的抑制剂是预防这种疾病的有前景的手段。
