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Uncoupling proteins in the mitochondrial defense against oxidative stress
Progress in Retinal and Eye Research ( IF 18.6 ) Pub Date : 2021-01-08 , DOI: 10.1016/j.preteyeres.2021.100941
Daniel T Hass 1 , Colin J Barnstable 2
Affiliation  

Oxidative stress is a major component of most major retinal diseases. Many extrinsic anti-oxidative strategies have been insufficient at counteracting one of the predominant intrinsic sources of reactive oxygen species (ROS), mitochondria. The proton gradient across the inner mitochondrial membrane is a key driving force for mitochondrial ROS production, and this gradient can be modulated by members of the mitochondrial uncoupling protein (UCP) family. Of the UCPs, UCP2 shows a widespread distribution and has been shown to uncouple oxidative phosphorylation, with concomitant decreases in ROS production. Genetic studies using transgenic and knockout mice have documented the ability of increased UCP2 activity to provide neuroprotection in models of a number of diseases, including retinal diseases, indicating that it is a strong candidate for a therapeutic target. Molecular studies have identified the structural mechanism of action of UCP2 and have detailed the ways in which its expression and activity can be controlled at the transcriptional, translational and posttranslational levels. These studies suggest a number of ways in control of UCP2 expression and activity can be used therapeutically for both acute and chronic conditions. The development of such therapeutic approaches will greatly increase the tools available to combat a broad range of serious retinal diseases.



中文翻译:

线粒体防御氧化应激中的解偶联蛋白

氧化应激是大多数主要视网膜疾病的主要组成部分。许多外在的抗氧化策略不足以抵消活性氧 (ROS) 的主要内在来源之一,即线粒体。穿过线粒体内膜的质子梯度是线粒体 ROS 产生的关键驱动力,这种梯度可以由线粒体解偶联蛋白 (UCP) 家族的成员调节。在 UCPs 中,UCP2 显示出广泛分布,并已被证明可以解耦氧化磷酸化,同时减少 ROS 的产生。使用转基因和基因敲除小鼠的基因研究已经证明了增加的 UCP2 活性在许多疾病模型中提供神经保护的能力,包括视网膜疾病,表明它是治疗靶点的有力候选者。分子研究已经确定了 UCP2 的结构作用机制,并详细说明了在转录、翻译和翻译后水平上控制其表达和活性的方式。这些研究表明,控制 UCP2 表达和活性的多种方法可用于治疗急性和慢性疾病。这种治疗方法的发展将大大增加可用于对抗广泛的严重视网膜疾病的工具。这些研究表明,控制 UCP2 表达和活性的多种方法可用于治疗急性和慢性疾病。这种治疗方法的发展将大大增加可用于对抗广泛的严重视网膜疾病的工具。这些研究表明,控制 UCP2 表达和活性的多种方法可用于治疗急性和慢性疾病。这种治疗方法的发展将大大增加可用于对抗广泛的严重视网膜疾病的工具。

更新日期:2021-01-08
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