Zhang Jialing, Zhang Ting, Zeng Shaoxue, Zhang Xinyuan, Zhou Fanfan, Gillies Mark C, Zhu Ling
Save Sight Institute, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
Department of Ocular Fundus Diseases, Beijing Tongren Eye Centre, Tongren Hospital, Capital Medical University, Beijing 100073, China.
Biomedicines. 2023 May 23;11(6):1512. doi: 10.3390/biomedicines11061512.
Age-related diseases, such as Parkinson's disease, Alzheimer's disease, cardiovascular diseases, cancers, and age-related macular disease, have become increasingly prominent as the population ages. Oxygen is essential for living organisms, but it may also cause disease when it is transformed into reactive oxygen species via biological processes in cells. Most of the production of ROS occurs in mitochondrial complexes I and III. The accumulation of ROS in cells causes oxidative stress, which plays a crucial role in human ageing and many diseases. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key antioxidant transcription factor that plays a central role in many diseases and ageing in general. It regulates many downstream antioxidative enzymes when cells are exposed to oxidative stress. A basic-region leucine zipper (bZIP) transcription factor, MAF, specifically the small MAF subfamily (sMAFs), forms heterodimers with Nrf2, which bind with Maf-recognition elements (MAREs) in response to oxidative stress. The role of this complex in the human retina remains unclear. This review summarises the current knowledge about Nrf2 and its downstream signalling, especially its cofactor-MAF, in ageing and diseases, with a focus on the retina. Since Nrf2 is the master regulator of redox homeostasis in cells, we hypothesise that targeting Nrf2 is a promising therapeutic approach for many age-related diseases.
随着人口老龄化，帕金森病、阿尔茨海默病、心血管疾病、癌症以及年龄相关性黄斑病变等与年龄相关的疾病日益突出。氧气对生物体至关重要，但当它通过细胞内的生物学过程转化为活性氧时也可能引发疾病。大部分活性氧的产生发生在线粒体复合物I和III中。细胞内活性氧的积累会导致氧化应激，氧化应激在人类衰老和许多疾病中起着关键作用。核因子红细胞2相关因子2（Nrf2）是一种关键的抗氧化转录因子，在许多疾病和整体衰老过程中发挥着核心作用。当细胞暴露于氧化应激时，它会调节许多下游抗氧化酶。一种碱性区域亮氨酸拉链（bZIP）转录因子MAF，特别是小MAF亚家族（sMAFs），与Nrf2形成异二聚体，在氧化应激反应中与Maf识别元件（MAREs）结合。这种复合物在人类视网膜中的作用仍不清楚。本综述总结了目前关于Nrf2及其下游信号传导，特别是其辅因子MAF在衰老和疾病中的知识，重点是视网膜。由于Nrf2是细胞内氧化还原稳态的主要调节因子，我们推测靶向Nrf2是治疗许多与年龄相关疾病的一种有前景的治疗方法。
