State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China.
State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.
Ageing Res Rev. 2020 Dec;64:101206. doi: 10.1016/j.arr.2020.101206. Epub 2020 Nov 2.
Alzheimer's disease (AD), an age-dependent neurodegenerative disorder, is the main cause of dementia. Common hallmarks of AD include the amyloid β-peptide (Aβ) aggregation, high levels of hyperphosphorylated tau protein (p-tau) and failure in redox homeostasis. To date, all proposed drugs affecting Aβ and/or p-tau have been failed in clinical trials. A decline in the expression of the transcription factor Nrf2 (nuclear factor-erythroid 2-p45 derived factor 2) and its driven genes (NQO1, HO-1, and GCLC), and alteration of the Nrf2-related pathways have been observed in AD brains. Nrf2 plays a critical role in maintaining cellular redox homeostasis and regulating inflammation response. Nrf2 activation also provides cytoprotection against increasing pathologies including neurodegenerative diseases. These lines of evidence imply that Nrf2 activation may be a novel AD treatment option. Interestingly, recent studies have also demonstrated that Nrf2 interferes with several key pathogenic processes in AD including Aβ and p-tau pathways. The current review aims to provide insights into the role of Nrf2 in AD. Also, we discuss the progress and challenges regarding the Nrf2 activators for AD treatment.
阿尔茨海默病（AD）是一种与年龄相关的神经退行性疾病，是痴呆的主要病因。AD 的常见特征包括淀粉样β肽（Aβ）聚集、高度磷酸化的 tau 蛋白（p-tau）水平升高以及氧化还原平衡失调。迄今为止，所有影响 Aβ和/或 p-tau 的拟议药物在临床试验中均已失败。在 AD 大脑中观察到转录因子 Nrf2（核因子-红细胞 2-p45 衍生因子 2）及其驱动基因（NQO1、HO-1 和 GCLC）的表达下降，以及 Nrf2 相关途径的改变。Nrf2 在维持细胞氧化还原平衡和调节炎症反应方面发挥着关键作用。Nrf2 的激活还为包括神经退行性疾病在内的不断增加的病理提供细胞保护。这些证据表明，Nrf2 的激活可能是一种新的 AD 治疗选择。有趣的是，最近的研究还表明，Nrf2 干扰 AD 中的几个关键致病过程，包括 Aβ和 p-tau 途径。本综述旨在深入了解 Nrf2 在 AD 中的作用。此外，我们还讨论了 Nrf2 激活剂在 AD 治疗方面的进展和挑战。
