Bjørklund Geir, Zou Lili, Peana Massimiliano, Chasapis Christos T, Hangan Tony, Lu Jun, Maes Michael
Council for Nutritional and Environmental Medicine, Toften 24, 8610 Mo i Rana, Norway.
Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang 443002, China.
Antioxidants (Basel). 2022 Oct 31;11(11):2161. doi: 10.3390/antiox11112161.
The thioredoxin system, consisting of thioredoxin (Trx), thioredoxin reductase (TrxR), and NADPH, plays a fundamental role in the control of antioxidant defenses, cell proliferation, redox states, and apoptosis. Aberrations in the Trx system may lead to increased oxidative stress toxicity and neurodegenerative processes. This study reviews the role of the Trx system in the pathophysiology and treatment of Alzheimer's, Parkinson's and Huntington's diseases, brain stroke, and multiple sclerosis. Trx system plays an important role in the pathophysiology of those disorders via multiple interactions through oxidative stress, apoptotic, neuro-immune, and pro-survival pathways. Multiple aberrations in Trx and TrxR systems related to other redox systems and their multiple reciprocal relationships with the neurodegenerative, neuro-inflammatory, and neuro-oxidative pathways are here analyzed. Genetic and environmental factors (nutrition, metals, and toxins) may impact the function of the Trx system, thereby contributing to neuropsychiatric disease. Aberrations in the Trx and TrxR systems could be a promising drug target to prevent and treat neurodegenerative, neuro-inflammatory, neuro-oxidative stress processes, and related brain disorders.
由硫氧还蛋白（Trx）、硫氧还蛋白还原酶（TrxR）和烟酰胺腺嘌呤二核苷酸磷酸（NADPH）组成的硫氧还蛋白系统在抗氧化防御、细胞增殖、氧化还原状态和细胞凋亡的调控中发挥着重要作用。硫氧还蛋白系统的异常可能导致氧化应激毒性增加和神经退行性变过程。本研究综述了硫氧还蛋白系统在阿尔茨海默病、帕金森病、亨廷顿病、脑卒中和多发性硬化症的病理生理学及治疗中的作用。硫氧还蛋白系统通过氧化应激、凋亡、神经免疫和促生存途径的多种相互作用，在这些疾病的病理生理学中发挥重要作用。本文分析了硫氧还蛋白和硫氧还蛋白还原酶系统中与其他氧化还原系统相关的多种异常及其与神经退行性、神经炎症和神经氧化途径的多重相互关系。遗传和环境因素（营养、金属和毒素）可能影响硫氧还蛋白系统的功能，从而导致神经精神疾病。硫氧还蛋白和硫氧还蛋白还原酶系统的异常可能是预防和治疗神经退行性、神经炎症、神经氧化应激过程及相关脑部疾病的一个有前景的药物靶点。
