Ren Xiaoyuan, Zou Lili, Zhang Xu, Branco Vasco, Wang Jun, Carvalho Cristina, Holmgren Arne, Lu Jun
1 Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet , Stockholm, Sweden .
2 Translational Neuroscience and Neural Regeneration and Repair Institute/Institute of Cell Therapy, The First Hospital of Yichang, Three Gorges University , Yichang, China .
Antioxid Redox Signal. 2017 Nov 1;27(13):989-1010. doi: 10.1089/ars.2016.6925. Epub 2017 May 18.
The thioredoxin (Trx) and glutathione (GSH) systems play important roles in maintaining the redox balance in the brain, a tissue that is prone to oxidative stress due to its high-energy demand. These two disulfide reductase systems are active in various areas of the brain and are considered to be critical antioxidant systems in the central nervous system (CNS). Various neuronal disorders have been characterized to have imbalanced redox homeostasis. Recent Advances: In addition to their detrimental effects, recent studies have highlighted that reactive oxygen species/reactive nitrogen species (ROS/RNS) act as critical signaling molecules by modifying thiols in proteins. The Trx and GSH systems, which reversibly regulate thiol modifications, regulate redox signaling involved in various biological events in the CNS.
In this review, we focus on the following: (i) how ROS/RNS are produced and mediate signaling in CNS; (ii) how Trx and GSH systems regulate redox signaling by catalyzing reversible thiol modifications; (iii) how dysfunction of the Trx and GSH systems causes alterations of cellular redox signaling in human neuronal diseases; and (iv) the effects of certain small molecules that target thiol-based signaling pathways in the CNS.
Further study on the roles of thiol-dependent redox systems in the CNS will improve our understanding of the pathogenesis of many human neuronal disorders and also help to develop novel protective and therapeutic strategies against neuronal diseases. Antioxid. Redox Signal. 27, 989-1010.
硫氧还蛋白（Trx）和谷胱甘肽（GSH）系统在维持大脑中的氧化还原平衡方面发挥着重要作用，大脑作为一个因高能量需求而易于发生氧化应激的组织。这两个二硫键还原酶系统在大脑的各个区域都有活性，并且被认为是中枢神经系统（CNS）中的关键抗氧化系统。各种神经元疾病的特征是氧化还原稳态失衡。
除了其有害影响外，最近的研究强调活性氧/活性氮物种（ROS/RNS）通过修饰蛋白质中的硫醇而作为关键信号分子。Trx和GSH系统可逆地调节硫醇修饰，调节中枢神经系统中各种生物事件所涉及的氧化还原信号传导。
在本综述中，我们关注以下几点：（i）ROS/RNS如何在中枢神经系统中产生并介导信号传导；（ii）Trx和GSH系统如何通过催化可逆的硫醇修饰来调节氧化还原信号传导；（iii）Trx和GSH系统的功能障碍如何在人类神经元疾病中导致细胞氧化还原信号传导的改变；以及（iv）某些靶向中枢神经系统中基于硫醇的信号通路的小分子的作用。
对中枢神经系统中硫醇依赖性氧化还原系统作用的进一步研究将增进我们对许多人类神经元疾病发病机制的理解，也有助于开发针对神经元疾病的新型保护和治疗策略。《抗氧化与氧化还原信号》，第27卷，989 - 1010页。
