Jia Jinjing, Xu Guangtao, Zhu Dongsheng, Liu Hongjun, Zeng Xiansi, Li Li
Research Center of Neuroscience, Jiaxing University Medical College, Jiaxing, China.
Department of Physiology, Jiaxing University Medical College, Jiaxing, China.
Antioxid Redox Signal. 2023 Feb;38(4-6):425-441. doi: 10.1089/ars.2022.0079. Epub 2022 Aug 12.
The thioredoxin system comprises thioredoxin (Trx), thioredoxin reductase (TrxR), and nicotinamide adenine dinucleotide phosphate, besides an endogenous Trx inhibitor, the thioredoxin-interacting protein (TXNIP). The Trx system plays critical roles in maintaining the redox homeostasis in the central nervous system (CNS), in which oxidative stress damage is prone to occurrence due to its high-energy demand. Increasing studies have demonstrated that the expression or activity of Trx/TrxR is usually decreased and that TXNIP expression is increased in patients with CNS diseases, including neurodegenerative diseases, cerebral ischemia, traumatic brain injury, and depression, as well as in their cellular and animal models. The compromise of Trx/TrxR enhances the susceptibility of neurons to related pathological state. Increased TXNIP not only enhances the inhibition of Trx activity, but also activates the NOD-like receptor protein 3 inflammasome, resulting in neuroinflammation in the brain. In this review, we highlight the sources of oxidative stress in the CNS. The expression and function of the Trx system are summarized in different CNS diseases. This review also mentions that some inducers of Trx show neuroprotection in CNS diseases. Accumulating evidence has demonstrated the important roles of the Trx system in CNS diseases, suggesting that the Trx system may be a promising therapeutic target for CNS diseases. Further study should aim to develop the most effective inducers of Trx and specific inhibitors of TXNIP and to apply them in the clinical trials for the treatment of CNS diseases. 38, 425-441.
硫氧还蛋白系统除了包含内源性硫氧还蛋白抑制剂硫氧还蛋白相互作用蛋白（TXNIP）外，还包括硫氧还蛋白（Trx）、硫氧还蛋白还原酶（TrxR）和烟酰胺腺嘌呤二核苷酸磷酸。硫氧还蛋白系统在维持中枢神经系统（CNS）的氧化还原稳态中发挥着关键作用，由于中枢神经系统对能量需求高，因此容易发生氧化应激损伤。越来越多的研究表明，在患有中枢神经系统疾病的患者中，包括神经退行性疾病、脑缺血、创伤性脑损伤和抑郁症，以及在其细胞和动物模型中，Trx/TrxR的表达或活性通常会降低，而TXNIP的表达会增加。Trx/TrxR功能的受损会增强神经元对相关病理状态的易感性。TXNIP的增加不仅增强了对Trx活性的抑制，还激活了NOD样受体蛋白3炎性小体，导致大脑中的神经炎症。在本综述中，我们重点介绍了中枢神经系统氧化应激的来源。总结了硫氧还蛋白系统在不同中枢神经系统疾病中的表达和功能。本综述还提到，一些硫氧还蛋白诱导剂在中枢神经系统疾病中显示出神经保护作用。越来越多的证据表明硫氧还蛋白系统在中枢神经系统疾病中发挥着重要作用，这表明硫氧还蛋白系统可能是中枢神经系统疾病一个有前景的治疗靶点。进一步的研究应致力于开发最有效的硫氧还蛋白诱导剂和TXNIP的特异性抑制剂，并将它们应用于治疗中枢神经系统疾病的临床试验中。38, 425 - 441。
