Department of Biological Sciences, Faculty of Basic & Applied Sciences, International Islamic University Islamabad, Pakistan.
Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
J Alzheimers Dis. 2024;99(s1):S97-S108. doi: 10.3233/JAD-230394.
Alzheimer's disease (AD) is the most common form of dementia and a public health problem. It exhibits significant oxidative stress and redox alterations. The antioxidant enzyme systems defend the cellular environment from oxidative stress. One of the redox systems is the thioredoxin system (TS), which exerts decisive control over the cellular redox environment. We aimed to review the protective effects of TS, which include thioredoxin (Trx), thioredoxin reductase (TrxR), and NADPH. In the following, we discussed the physiological functioning and the role of the TS in maintaining the cellular redox-homeostasis in the AD-damaged brain. Trx protects the cellular environment from oxidative stress, while TrxR is crucial for the cellular detoxification of reactive oxygen species in the brain. However, TS dysregulation increases the susceptibility to cellular death. The changes in Trx and TrxR levels are significantly associated with AD progression. Though the data from human, animal, and cellular models support the neuroprotective role of TS in the brain of AD patients, the translational potential of these findings to clinical settings is not yet applied. This review summarizes the current knowledge on the emerging role of the TrxR-Trx system in AD.
阿尔茨海默病（AD）是最常见的痴呆症形式，也是一个公共卫生问题。它表现出明显的氧化应激和氧化还原改变。抗氧化酶系统可以保护细胞环境免受氧化应激。氧化还原系统之一是硫氧还蛋白系统（TS），它对细胞的氧化还原环境具有决定性的控制作用。我们旨在回顾 TS 的保护作用，包括硫氧还蛋白（Trx）、硫氧还蛋白还原酶（TrxR）和 NADPH。在下面，我们讨论了 TS 在维持 AD 损伤大脑中的细胞氧化还原平衡方面的生理功能和作用。Trx 可以保护细胞环境免受氧化应激，而 TrxR 对于大脑中活性氧的细胞解毒至关重要。然而，TS 失调会增加细胞死亡的易感性。Trx 和 TrxR 水平的变化与 AD 进展显著相关。尽管来自人类、动物和细胞模型的数据支持 TS 在 AD 患者大脑中的神经保护作用，但这些发现转化为临床应用的潜力尚未得到应用。本综述总结了 TrxR-Trx 系统在 AD 中新兴作用的最新知识。
