Wang Pei, Wang Fang, Ni Lan, Wu Pengfei, Chen Jianguo
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan 430030, China.
Acta Pharm Sin B. 2021 Mar;11(3):599-608. doi: 10.1016/j.apsb.2020.11.012. Epub 2020 Nov 24.
Redox-altered plasticity refers to redox-dependent reversible changes in synaptic plasticity altering functions of key proteins, such as -methyl-d-aspartate receptor (NMDAR). Age-related cognitive disorders includes Alzheimer's disease (AD), vascular dementia (VD), and age-associated memory impairment (AAMI). Based on the critical role of NMDAR-dependent long-term potentiation (LTP) in memory, the increase of reactive oxygen species in cognitive disorders, and the sensitivity of NMDAR to the redox status, converging lines have suggested the redox-altered NMDAR-dependent plasticity might underlie the synaptic dysfunctions associated with cognitive disorders. In this review, we summarize the involvement of redox-altered plasticity in cognitive disorders by presenting the available evidence. According to reports from our laboratory and other groups, this "redox-altered plasticity" is more similar to functional changes rather than organic injuries, and strategies targeting redox-altered plasticity using pharmacological agents might reverse synaptic dysfunctions and memory abnormalities in the early stage of cognitive disorders. Targeting redox modifications for NMDARs may serve as a novel therapeutic strategy for memory deficits.
氧化还原改变的可塑性是指突触可塑性中依赖氧化还原的可逆变化，这种变化会改变关键蛋白的功能，如N-甲基-D-天冬氨酸受体（NMDAR）。与年龄相关的认知障碍包括阿尔茨海默病（AD）、血管性痴呆（VD）和年龄相关性记忆损害（AAMI）。基于依赖NMDAR的长时程增强（LTP）在记忆中的关键作用、认知障碍中活性氧的增加以及NMDAR对氧化还原状态的敏感性，多条线索表明氧化还原改变的依赖NMDAR的可塑性可能是与认知障碍相关的突触功能障碍的基础。在本综述中，我们通过展示现有证据来总结氧化还原改变的可塑性在认知障碍中的作用。根据我们实验室和其他团队的报告，这种“氧化还原改变的可塑性”更类似于功能变化而非器质性损伤，并且使用药物靶向氧化还原改变的可塑性的策略可能会在认知障碍的早期阶段逆转突触功能障碍和记忆异常。针对NMDAR的氧化还原修饰进行靶向治疗可能成为治疗记忆缺陷的一种新策略。
