Glutathione as a Redox Biomarker in Mitochondrial Disease-Implications for Therapy.
Glutathione as a Redox Biomarker in Mitochondrial Disease-Implications for Therapy.
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DOI：
10.3390/jcm6050050
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发表时间：
2017-05-03
影响因子：
3.9
通讯作者：
Cowan TM
中科院分区：
文献类型：
--
作者：
Enns GM;Cowan TM
测量线粒体功能障碍能力的技术进步为线粒体疾病发病机制提供了新的见解，沿着新的工具来客观地评估线粒体疾病患者的临床状态。谷胱甘肽（1-β-谷氨酰基-1-半胱氨酰甘氨酸）是最丰富的细胞内硫醇，并且如由氧化型谷胱甘肽（GSSG）和还原型谷胱甘肽（GSH）的水平以及GSH/GSSG比率所反映的细胞内氧化还原状态被认为是细胞健康的重要指示。量化受影响患者的线粒体功能障碍的能力不仅有助于常规护理，而且还可以改善旨在开发新疗法的合理临床试验设计。事实上，由于多种疾病都与线粒体电子传递链的原发性或继发性缺陷和氧化还原失衡有关，因此开发有可能改善细胞内谷胱甘肽状态的线粒体疗法一直是过去几年多项临床试验的焦点。本综述还将讨论增加细胞内谷胱甘肽的潜在疗法，重点是EPI-743（α-生育三烯酚醌），一种似乎能够调节氧化还原酶活性的化合物，特别是NAD（P）H：醌氧化还原酶1。
Technical advances in the ability to measure mitochondrial dysfunction are providing new insights into mitochondrial disease pathogenesis, along with new tools to objectively evaluate the clinical status of mitochondrial disease patients. Glutathione (l-ϒ-glutamyl-l-cysteinylglycine) is the most abundant intracellular thiol, and the intracellular redox state, as reflected by levels of oxidized (GSSG) and reduced (GSH) glutathione, as well as the GSH/GSSG ratio, is considered to be an important indication of cellular health. The ability to quantify mitochondrial dysfunction in an affected patient will not only help with routine care, but also improve rational clinical trial design aimed at developing new therapies. Indeed, because multiple disorders have been associated with either primary or secondary deficiency of the mitochondrial electron transport chain and redox imbalance, developing mitochondrial therapies that have the potential to improve the intracellular glutathione status has been a focus of several clinical trials over the past few years. This review will also discuss potential therapies to increase intracellular glutathione with a focus on EPI-743 (α-tocotrienol quinone), a compound that appears to have the ability to modulate the activity of oxidoreductases, in particular NAD(P)H:quinone oxidoreductase 1.