Petri Susanne, Körner Sonja, Kiaei Mahmoud
Department of Neurology, Hannover Medical School, Hannover, Germany.
Neurol Res Int. 2012;2012:878030. doi: 10.1155/2012/878030. Epub 2012 Sep 20.
Nrf2 (nuclear erythroid 2-related factor 2) is a basic region leucine-zipper transcription factor which binds to the antioxidant response element (ARE) and thereby regulates the expression of a large battery of genes involved in the cellular antioxidant and anti-inflammatory defence as well as mitochondrial protection. As oxidative stress, inflammation and mitochondrial dysfunctions have been identified as important pathomechanisms in amyotrophic lateral sclerosis (ALS), this signaling cascade has gained interest both with respect to ALS pathogenesis and therapy. Nrf2 and Keap1 expressions are reduced in motor neurons in postmortem ALS tissue. Nrf2-activating compounds have shown therapeutic efficacy in the ALS mouse model and other neurodegenerative disease models. Alterations in Nrf2 and Keap1 expression and dysregulation of the Nrf2/ARE signalling program could contribute to the chronic motor neuron degeneration in ALS and other neurodegenerative diseases. Therefore, Nrf2 emerges as a key neuroprotective molecule in neurodegenerative diseases. Our recent studies strongly support that the Nrf2/ARE signalling pathway is an important mediator of neuroprotection and therefore represents a promising target for development of novel therapies against ALS, Parkinson's disease (PD), Huntington's disease (HD), and Alzheimer's disease (AD).
核红细胞2相关因子2（Nrf2）是一种碱性区域亮氨酸拉链转录因子，它与抗氧化反应元件（ARE）结合，从而调节大量参与细胞抗氧化、抗炎防御以及线粒体保护的基因的表达。由于氧化应激、炎症和线粒体功能障碍已被确定为肌萎缩侧索硬化症（ALS）的重要发病机制，因此该信号级联反应在ALS发病机制和治疗方面都引起了关注。在ALS患者死后的组织中，运动神经元中的Nrf2和Keap1表达降低。激活Nrf2的化合物在ALS小鼠模型和其他神经退行性疾病模型中显示出治疗效果。Nrf2和Keap1表达的改变以及Nrf2/ARE信号程序的失调可能导致ALS和其他神经退行性疾病中慢性运动神经元变性。因此，Nrf2成为神经退行性疾病中的关键神经保护分子。我们最近的研究有力地支持了Nrf2/ARE信号通路是神经保护的重要介质，因此是开发针对ALS、帕金森病（PD）、亨廷顿病（HD）和阿尔茨海默病（AD）的新型疗法的有希望的靶点。
