Department of Neurology, Oregon Health and Science University, Portland, OR, USA.
ASN Neuro. 2020 Jan-Dec;12:1759091419899782. doi: 10.1177/1759091419899782.
Increased reactive oxygen species production and oxidative stress have been implicated in the pathogenesis of numerous neurodegenerative conditions including among others Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Friedrich’s ataxia, multiple sclerosis, and stroke. The endogenous antioxidant response pathway protects cells from oxidative stress by increasing the expression of cytoprotective enzymes and is regulated by the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2). In addition to regulating the expression of antioxidant genes, NRF2 has also been shown to exert anti-inflammatory effects and modulate both mitochondrial function and biogenesis. This is because mitochondrial dysfunction and neuroinflammation are features of many neurodegenerative diseases as well NRF2 has emerged as a promising therapeutic target. Here, we review evidence for a beneficial role of NRF2 in neurodegenerative conditions and the potential of specific NRF2 activators as therapeutic agents.
活性氧物种的产生增加和氧化应激与许多神经退行性疾病的发病机制有关，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、多发性硬化症和中风等。内源性抗氧化反应途径通过增加细胞保护酶的表达来保护细胞免受氧化应激的影响，并且受转录因子红细胞生成 2 相关因子 2（NRF2）的调节。除了调节抗氧化基因的表达外，NRF2 还显示出抗炎作用，并调节线粒体功能和生物发生。这是因为线粒体功能障碍和神经炎症是许多神经退行性疾病的特征，并且 NRF2 已成为有前途的治疗靶点。在这里，我们回顾了 NRF2 在神经退行性疾病中的有益作用的证据，以及特定的 NRF2 激活剂作为治疗剂的潜力。
