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非编码 RNA 调控线粒体功能和氧化应激反应作为对抗年龄相关性黄斑变性 (AMD) 的潜在靶点。

Non-Coding RNAs Regulating Mitochondrial Functions and the Oxidative Stress Response as Putative Targets against Age-Related Macular Degeneration (AMD).

机构信息

Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.

Department of Molecular Genetics, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.

出版信息

Int J Mol Sci. 2023 Jan 30;24(3):2636. doi: 10.3390/ijms24032636.

Abstract

Age-related macular degeneration (AMD) is an ever-increasing, insidious disease which reduces the quality of life of millions of elderly people around the world. AMD is characterised by damage to the retinal pigment epithelium (RPE) in the macula region of the retina. The origins of this multi-factorial disease are complex and still not fully understood. Oxidative stress and mitochondrial imbalance in the RPE are believed to be important factors in the development of AMD. In this review, the regulation of the mitochondrial function and antioxidant stress response by non-coding RNAs (ncRNAs), newly emerged epigenetic factors, is discussed. These molecules include microRNAs, long non-coding RNAs, and circular non-coding RNAs. They act mainly as mRNA suppressors, controllers of other ncRNAs, or by interacting with proteins. We include here examples of these RNA molecules which affect various mitochondrial processes and antioxidant signaling of the cell. As a future prospect, the possibility to manipulate these ncRNAs to strengthen mitochondrial and antioxidant response functions is discussed. Non-coding RNAs could be used as potential diagnostic markers for AMD, and in the future, also as therapeutic targets, either by suppressing or increasing their expression. In addition to AMD, it is possible that non-coding RNAs could be regulators in other oxidative stress-related degenerative diseases.

摘要

年龄相关性黄斑变性(AMD)是一种日益严重、隐匿的疾病,它降低了全球数以百万计老年人的生活质量。AMD 的特征是视网膜黄斑区的视网膜色素上皮(RPE)受损。这种多因素疾病的起源复杂,仍不完全清楚。RPE 中的氧化应激和线粒体失衡被认为是 AMD 发展的重要因素。在这篇综述中,讨论了非编码 RNA(ncRNA)作为新兴的表观遗传因子对线粒体功能和抗氧化应激反应的调节。这些分子包括 microRNAs、长非编码 RNA 和环状非编码 RNA。它们主要作为 mRNA 抑制剂、其他 ncRNA 的控制器,或通过与蛋白质相互作用发挥作用。我们在这里包括了这些 RNA 分子影响各种线粒体过程和细胞抗氧化信号的例子。作为未来的展望,讨论了操纵这些 ncRNA 以增强线粒体和抗氧化反应功能的可能性。非编码 RNA 可以作为 AMD 的潜在诊断标志物,并且在未来也可以作为治疗靶点,通过抑制或增加其表达。除了 AMD,非编码 RNA 也可能是其他氧化应激相关退行性疾病的调节剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cb/9917342/98ee4ecbc797/ijms-24-02636-g001.jpg

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