Institute of Pharmaceutical Research, GLA University, Mathura-281406, U.P., India.
School of Pharmaceutical Sciences, MVN University, Palwal-121105, Haryana, India.
Protein Pept Lett. 2022;29(8):676-691. doi: 10.2174/0929866529666220622124253.
Nuclear factor erythroid-2-related factor 2 (Nrf2), an inducible transcription factor in phase II metabolic reactions, as well as xenobiotic response pathway, is referred to as 'master regulator' in anti-oxidant, anti-inflammatory, and xenobiotic detoxification processes. The activity of Nrf2 is tightly regulated by KEAP1, which promotes ubiquitination, followed by degradation under homeostatic conditions and also allows Nrf2 to escape ubiquitination, accumulate within the cell, and translocate in the nucleus upon exposure to the stresses. The Nrf2 pathway has shown an intrinsic mechanism of defense against oxidative stress (OS). It emerged as a promising therapeutic target as both inducers and as there is an increasing number of evidence for the protective role of the Nrf2-ARE pathway towards exacerbations of ROS generation as well as OS, mitochondrial dysfunction as well as prolonged neuroinflammation is a prevalent pathophysiological process rooted in brain-related disorders. Elevated concentrations of ROS generation and OS have been linked to the pathophysiology of a diverse array of brain related disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, Friedrich's ataxia, multiple sclerosis, and epilepsy. Further, it not only modulates the articulation of anti-oxidant genes but has often been associated with implicating anti-inflammatory consequences as well as regulating mitochondrial functionalities and biogenesis. Therefore, Nrf2 can be considered a potential therapeutic target for the regimen of various brain-related disorders.
核因子红细胞 2 相关因子 2（Nrf2）是一种诱导型转录因子，参与二期代谢反应和外源物反应途径，被称为抗氧化、抗炎和外源物解毒过程中的“主调控因子”。Nrf2 的活性受到 KEAP1 的紧密调控，KEAP1 促进其泛素化，在稳态条件下导致其降解，同时也允许 Nrf2 逃避泛素化，在细胞内积累，并在暴露于应激时易位到细胞核内。Nrf2 途径具有内在的抗氧化应激（OS）防御机制。它作为诱导剂具有很大的治疗潜力，并且越来越多的证据表明，Nrf2-ARE 途径对 ROS 生成和 OS、线粒体功能障碍以及长期神经炎症的加剧具有保护作用，这是一种普遍的病理生理过程，存在于与大脑相关的疾病中。ROS 生成和 OS 的升高与多种与大脑相关的疾病的病理生理学有关，包括阿尔茨海默病、帕金森病、亨廷顿病、弗里德里希共济失调、多发性硬化症和癫痫。此外，它不仅调节抗氧化基因的表达，而且常常与炎症反应以及调节线粒体功能和生物发生有关。因此，Nrf2 可以被视为各种与大脑相关的疾病治疗的潜在靶点。
