Nrf2在阿尔茨海默病中的研究现状

The Research Progress of Nrf2 in Alzheimer′s Disease

阿尔茨海默病(Alzheimer's disease,AD)是最常见的神经系统变性疾病,主要病理特征为细胞外老年斑(senile plaques,SP)和细胞内神经原纤维缠结(neurofibrillary tangles,NFT)形成.但其发病机制不清,涉及多种病理学变化如炎症反应、氧化应激、线粒体功能障碍、细胞凋亡以及突触功能障碍等.核因子E2相关因子2(nuclear factor erythroid 2-related factor 2,Nrf2)是经典的调控机体抗氧化应激反应的核转录因子.Nrf2激活后诱导抗氧化蛋白的表达,提高机体的抗氧化应激能力.随着Nrf2抗氧化应激作用研究的深入,发现Nrf2不仅能够通过抗氧化应激延缓AD的发生发展,且在AD的病理性沉积物的清除、抗炎、抗凋亡、神经营养等方面扮演着重要的角色.近年来,由于多种针对单一靶点的抗AD药物临床试验的失败,有学者提出Nrf2可能是实现AD多靶点疗法的重要因子.因此,本文对Nrf2在AD中的研究现状做一综述,为寻找治疗AD潜在的生物学靶点提供理论依据.

Alzheimer＇s disease （AD） is the most common neurodegenerative diseases characterized by the accumulation of two hallmark pathologies, extraneuronal senile plaques and intraneuronal neurofibrillary tangles. Although the exact mechanisms that trigger the pathological alterations of AD are still not clear, most studies have suggested a variety of pathological changes such as inflammation, oxidative stress, mitochondrial dysfunction, apoptosis and synaptic dysfunction, etc. The transcription factor Nrf2 （nuclear factor erythroid 2-related factor 2） is activated by oxidative stress and regulates the expression of a variety of antioxidant enzymes and proteins that exert cytoprotective effects against oxidative stress. Numerous studies have addressed the role of Nrf2 against oxidative stress. Further, recent findings concerning that Nrf2 not only regulates antioxidant proteins but also regulates the genes associated with anti-inflammatory, anti-apoptotic and nerve growth factor signaling in AD. In addition, activation of the Nrf2 pathway may have the effect of anti-amyloidogenic and reduces the levels of phosphorylated tau. Recently all new anti-AD drugs focused on a single target have failed, so researchers put forward that activation of Nrf2 may be a good treatment for AD through simultaneous modulation of numerous pathways involved in AD pathogenesis. Here in this review we summarize the research status of Nrf2 in AD.