Zhang Xiangyu, Li Hengzhen, Chen Lin, Wu Yuxiang, Li Yusheng
Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Genes Dis. 2023 Nov 27;11(6):101180. doi: 10.1016/j.gendis.2023.101180. eCollection 2024 Nov.
The NRF2 pathway is a metabolic- and redox-sensitive signaling axis in which the transcription factor controls the expression of a multitude of genes that enable cells to survive environmental stressors, such as oxidative stress, mainly by inducing the expression of cytoprotective genes. Basal NRF2 levels are maintained under normal physiological conditions, but when exposed to oxidative stress, cells activate the NRF2 pathway, which is crucial for supporting cell survival. Recently, the NRF2 pathway has been found to have novel functions in metabolic regulation and interplay with other signaling pathways, offering novel insights into the treatment of various diseases. Numerous studies have shown that targeting its pathway can effectively investigate the development and progression of age-related musculoskeletal diseases, such as sarcopenia, osteoporosis, osteoarthritis, and intervertebral disc degeneration. Appropriate regulation of the NRF2 pathway flux holds promise as a means to improve musculoskeletal function, thereby providing a new avenue for drug treatment of age-related musculoskeletal diseases in clinical settings. The review summarized an overview of the relationship between NRF2 and cellular processes such as oxidative stress, apoptosis, inflammation, mitochondrial dysfunction, ferroptosis, and autophagy, and explores the potential of targeted NRF2 regulation in the treatment of age-related musculoskeletal diseases.
NRF2通路是一条对代谢和氧化还原敏感的信号轴，其中转录因子控制众多基因的表达，这些基因主要通过诱导细胞保护基因的表达，使细胞能够在诸如氧化应激等环境应激因素下存活。在正常生理条件下，NRF2的基础水平得以维持，但当细胞暴露于氧化应激时，会激活NRF2通路，这对于支持细胞存活至关重要。最近，人们发现NRF2通路在代谢调节以及与其他信号通路的相互作用中具有新功能，为各种疾病的治疗提供了新的见解。大量研究表明，靶向该通路能够有效地研究与年龄相关的肌肉骨骼疾病（如肌肉减少症、骨质疏松症、骨关节炎和椎间盘退变）的发生和发展。对NRF2通路通量进行适当调节有望改善肌肉骨骼功能，从而为临床治疗与年龄相关的肌肉骨骼疾病提供新的药物治疗途径。本综述总结了NRF2与氧化应激、细胞凋亡、炎症、线粒体功能障碍、铁死亡和自噬等细胞过程之间关系的概述，并探讨了靶向NRF2调节在治疗与年龄相关的肌肉骨骼疾病中的潜力。
