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Keap1/Nrf2信号通路在神经退行性疾病中的作用。

Role of the Keap1/Nrf2 pathway in neurodegenerative diseases.

作者信息

Yamazaki Hiromi, Tanji Kunikazu, Wakabayashi Koichi, Matsuura Shin, Itoh Ken

机构信息

Department of Stress Response Science, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.

出版信息

Pathol Int. 2015 May;65(5):210-9. doi: 10.1111/pin.12261. Epub 2015 Feb 23.

Abstract

As the elderly population increases, a growing number of individuals suffer from age-associated neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Oxidative stress is considered to play a crucial role in the pathogenesis of age-related diseases. 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 in age-related diseases, including neurodegenerative diseases, using animal or in vitro cell culture models. Here, we introduce the role of oxidative stress in the pathogenesis of neurodegenerative diseases and critically examine the recent findings concerning the role for Nrf2 in the amelioration of AD and PD. Nrf2 not only regulates antioxidant proteins but also regulates the genes associated with autophagy and nerve growth factor signaling. Current research unequivocally demonstrates that the activation of the Nrf2 pathway is a promising novel strategy for the prevention and modification of neurodegenerative diseases.

摘要

随着老年人口的增加,越来越多的人患有与年龄相关的神经退行性疾病,如阿尔茨海默病(AD)和帕金森病(PD)。氧化应激被认为在与年龄相关疾病的发病机制中起关键作用。转录因子Nrf2(核因子红细胞2相关因子2)被氧化应激激活,并调节多种抗氧化酶和蛋白质的表达,这些酶和蛋白质对氧化应激发挥细胞保护作用。许多研究使用动物或体外细胞培养模型探讨了Nrf2在包括神经退行性疾病在内的与年龄相关疾病中的作用。在这里,我们介绍氧化应激在神经退行性疾病发病机制中的作用,并严格审视关于Nrf2在改善AD和PD方面作用的最新研究结果。Nrf2不仅调节抗氧化蛋白,还调节与自噬和神经生长因子信号传导相关的基因。目前的研究明确表明,Nrf2途径的激活是预防和改善神经退行性疾病的一种有前景的新策略。

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