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慢性肾脏病的线粒体靶向治疗策略

Mitochondria-targeting therapeutic strategies for chronic kidney disease.

作者信息

Sun Annie, Pollock Carol A, Huang Chunling

机构信息

Kolling Institute, Sydney Medical School Northern, Faculty of Medicine and Health, University of Sydney, Royal North Shore Hospital, St Leonards, New South Wales, Australia.

Kolling Institute, Sydney Medical School Northern, Faculty of Medicine and Health, University of Sydney, Royal North Shore Hospital, St Leonards, New South Wales, Australia.

出版信息

Biochem Pharmacol. 2025 Jan;231:116669. doi: 10.1016/j.bcp.2024.116669. Epub 2024 Nov 27.

Abstract

Chronic kidney disease (CKD) is a multifactorial health issue characterised by kidney impairment that has significant morbidity and mortality in the global population. Current treatments for CKD fail to prevent progression to end-stage kidney disease, where management is limited to renal replacement therapy or kidney transplantation. Mitochondrial dysfunction has been implicated in the pathogenesis of CKD and can be broadly categorised into abnormalities related to excessive oxidative stress, reduced mitochondrial biogenesis, excess mitochondrial fission and dysregulated mitophagy. Mitochondria-targeting therapeutic strategies target many of the outlined mechanisms of mitochondrial dysfunction, and an overview of recent evidence for mitochondria-targeting therapeutic strategies is explored in this review, including naturally derived compounds and novel approaches such as fusion proteins. Mitochondria-targeting therapeutic strategies using these approaches show the potential to stabilise or improve renal function, and clinical studies are needed to further confirm their safety and efficacy in human contexts.

摘要

慢性肾脏病(CKD)是一个多因素的健康问题,其特征为肾脏功能受损,在全球人口中具有显著的发病率和死亡率。目前针对CKD的治疗方法无法预防疾病进展至终末期肾病,而终末期肾病的治疗仅限于肾脏替代疗法或肾移植。线粒体功能障碍与CKD的发病机制有关,可大致分为与氧化应激过度、线粒体生物发生减少、线粒体过度裂变和线粒体自噬失调相关的异常。针对线粒体的治疗策略针对了线粒体功能障碍的许多上述机制,本文综述了针对线粒体治疗策略的最新证据,包括天然衍生化合物和融合蛋白等新方法。使用这些方法的针对线粒体的治疗策略显示出稳定或改善肾功能的潜力,需要进行临床研究以进一步证实其在人体中的安全性和有效性。

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