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利用Nur77的线粒体凋亡途径:一种有前景的靶向疾病干预治疗策略。

Harnessing Nur77's mitochondrial apoptotic pathway: A promising therapeutic strategy for targeted disease intervention.

作者信息

Fu Ruihai, Ling Dandan, Zhang Qiqi, Jiang Aifang, Pang Haiyan

机构信息

School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong Province, PR China.

Clinical Research Center for Placental Medicine In Hunan Province, Changsha City, Hunan Province, PR China; Department of Obstetrics, Hunan Provincial Maternal and Child Health Care Hospital, Changsha City, Hunan Province, PR China.

出版信息

Biomed Pharmacother. 2025 Jun;187:118091. doi: 10.1016/j.biopha.2025.118091. Epub 2025 Apr 25.

DOI:10.1016/j.biopha.2025.118091
PMID:40286599
Abstract

The role of mitochondria in disease development cannot be overlooked, and the targeting of mitochondria for the treatment of disease has emerged as a significant area of research in recent years. Mitochondria are the control center of the intrinsic apoptotic pathway, and their normal functions are finely regulated by a series of complex mechanisms. The nuclear receptor Nur77 is closely related to the functions of the mitochondria and is an active pro-apoptotic member of the nuclear receptor superfamily. The translocation of Nur77 to the mitochondria can promote the conversion of the anti-apoptotic protein Bcl-2 to a pro-apoptotic state, disrupt the balance between mitochondrial fission and fusion, and inhibit mitophagy. These effects lead to irreversible damage to mitochondria and apoptosis, ultimately accelerating the progression of the disease. Here, we review the mechanism and targeted drug development of the mitochondrial apoptosis pathway activated by Nur77 in human diseases, helping to understand the new advances in disease treatment.

摘要

线粒体在疾病发展中的作用不容忽视,近年来,针对线粒体进行疾病治疗已成为一个重要的研究领域。线粒体是内源性凋亡途径的控制中心,其正常功能受到一系列复杂机制的精细调控。核受体Nur77与线粒体功能密切相关,是核受体超家族中一个活跃的促凋亡成员。Nur77向线粒体的转位可促进抗凋亡蛋白Bcl-2向促凋亡状态的转变,破坏线粒体裂变与融合之间的平衡,并抑制线粒体自噬。这些效应导致线粒体的不可逆损伤和凋亡,最终加速疾病的进展。在此,我们综述了Nur77激活的线粒体凋亡途径在人类疾病中的机制及靶向药物开发,有助于了解疾病治疗的新进展。

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