Enns Gregory M, Cowan Tina M
Departments of Pediatrics and Pathology, Stanford University, 300 Pasteur Drive, H-315, Stanford, CA 94005-5208, USA.
J Clin Med. 2017 May 3;6(5):50. doi: 10.3390/jcm6050050.
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.
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见解，同时也带来了客观评估线粒体疾病患者临床状况的新工具。谷胱甘肽（L-γ-谷氨酰-L-半胱氨酰甘氨酸）是细胞内最丰富的硫醇，细胞内氧化还原状态，由氧化型（GSSG）和还原型（GSH）谷胱甘肽水平以及GSH/GSSG比值反映，被认为是细胞健康的重要指标。量化受影响患者线粒体功能障碍的能力不仅有助于日常护理，还能改善旨在开发新疗法的合理临床试验设计。事实上，由于多种疾病与线粒体电子传递链的原发性或继发性缺陷以及氧化还原失衡有关，开发有可能改善细胞内谷胱甘肽状态的线粒体疗法在过去几年一直是多项临床试验的重点。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），一种似乎有能力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。
