Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India.
Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia.
Life Sci. 2024 Nov 15;357:123056. doi: 10.1016/j.lfs.2024.123056. Epub 2024 Sep 12.
Mitochondrial dysfunction and cognitive impairment are widespread phenomena among the elderly, being crucial factors that contribute to neurodegenerative diseases. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important regulator of cellular defense systems, including that against oxidative stress. As such, increased Nrf2 activity may serve as a strategy to avert mitochondrial dysfunction and cognitive decline. Scientific data on Nrf2-mediated neuroprotection was collected from PubMed, Google Scholar, and Science Direct, specifically addressing mitochondrial dysfunction and cognitive impairment in older people. Search terms included "Nrf2", "mitochondrial dysfunction," "cognitive impairment," and "neuroprotection." Studies focusing on in vitro and in vivo models and clinical investigations were included to review Nrf2's therapeutic potential comprehensively. The relative studies have demonstrated that increased Nrf2 activity could improve mitochondrial performance, decrease oxidative pressure, and mitigate cognitive impairment. To a large extent, this is achieved through the modulation of critical cellular signalling pathways such as the Keap1/Nrf2 pathway, mitochondrial biogenesis, and neuroinflammatory responses. The present review summarizes the recent progress in comprehending the molecular mechanisms regarding the neuroprotective benefits mediated by Nrf2 through its substantial role against mitochondrial dysfunction and cognitive impairment. This review also emphasizes Nrf2-target pathways and their contribution to cognitive function improvement and rescue from mitochondria-related abnormalities as treatment strategies for neurodegenerative diseases that often affect elderly individuals.
线粒体功能障碍和认知障碍在老年人中普遍存在，是导致神经退行性疾病的重要因素。核因子红细胞 2 相关因子 2（Nrf2）是细胞防御系统的重要调节剂，包括抗氧化应激。因此，增加 Nrf2 的活性可能是避免线粒体功能障碍和认知能力下降的一种策略。从 PubMed、Google Scholar 和 Science Direct 收集了关于 Nrf2 介导的神经保护的科学数据，专门针对老年人的线粒体功能障碍和认知障碍。搜索词包括“Nrf2”、“线粒体功能障碍”、“认知障碍”和“神经保护”。纳入了关注体外和体内模型以及临床研究的研究，以全面综述 Nrf2 的治疗潜力。相关研究表明，增加 Nrf2 的活性可以改善线粒体功能，降低氧化压力，减轻认知障碍。在很大程度上，这是通过调节关键的细胞信号通路来实现的，如 Keap1/Nrf2 通路、线粒体生物发生和神经炎症反应。本综述总结了近年来对 Nrf2 通过其对线粒体功能障碍和认知障碍的显著作用介导的神经保护益处的分子机制的理解进展。本综述还强调了 Nrf2 靶向途径及其对认知功能改善和从与线粒体相关的异常中恢复的贡献，作为治疗常影响老年人的神经退行性疾病的策略。
