Uncoupling proteins in the mitochondrial defense against oxidative stress.
Uncoupling proteins in the mitochondrial defense against oxidative stress.
复制标题
DOI：
10.1016/j.preteyeres.2021.100941
复制
发表时间：
2021-07
影响因子：
17.8
通讯作者：
Barnstable CJ
中科院分区：
文献类型：
--
作者：
Hass DT;Barnstable CJ
氧化应激是大多数主要视网膜疾病的主要组成部分。许多外源性抗氧化策略不足以抵消活性氧（ROS）的主要内在来源之一，线粒体。线粒体内膜上的质子梯度是线粒体ROS产生的关键驱动力，这种梯度可以通过线粒体解偶联蛋白（UCP）家族的成员进行调节。在UCPs中，UCP2显示出广泛的分布，并且已显示出解偶联氧化磷酸化，伴随着ROS产生的减少。使用转基因和基因敲除小鼠的遗传研究已经证明了UCP2活性增加在许多疾病模型中提供神经保护的能力，包括视网膜疾病，这表明它是治疗靶点的强有力候选者。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表达和活性的许多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各种严重视网膜疾病的工具。
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.
登录
查看更多内容
影响因子：
15.9
作者：
Barber, AJ;Lieth, E;Gardner, TW
通讯作者：
Gardner, TW
影响因子：
4.7
作者：
Alam, ZI;Jenner, A;Halliwell, B
通讯作者：
Halliwell, B
影响因子：
3.7
作者：
Bogdanov P;Corraliza L;Villena JA;Carvalho AR;Garcia-Arumí J;Ramos D;Ruberte J;Simó R;Hernández C
通讯作者：
Hernández C
影响因子：
4.4
作者：
Barber, Alistair J.;Gardner, Thomas W.;Abcouwer, Steven F.
通讯作者：
Abcouwer, Steven F.
DOI：
10.1016/j.bbamcr.2016.04.013
发表时间：
2016-10-01
影响因子：
5.1
作者：
Bouillaud, Frederic;Alves-Guerra, Marie-Clotilde;Ricquier, Daniel
通讯作者：
Ricquier, Daniel