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Targeting the NMDA receptor subunit NR2B for treating or preventing age-related memory decline

机译：靶向NMDA受体亚基NR2B以治疗或预防与年龄有关的记忆衰退

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Introduction: Age-related memory loss is believed to be a result of reduced synaptic plasticity, including changes in the NR2 subunit composition of the NMDA receptor. It is known that endogenous NR2B subunits decrease as the brain ages, whereas transgenic upregulation of NR2B enhances synaptic plasticity and learning and memory in several animal species. Accumulating evidence suggests that elevated brain magnesium levels, via dietary supplementation, can boost NR2B in the brain, consequently reversing memory deficits and enhancing cognitive abilities.Areas covered: This review highlights the convergent molecular mechanisms via the NR2B pathway as a useful strategy for treating age-related memory loss. A dietary approach, via oral intake of a novel compound, magnesium L-threonate (MgT), to boost NR2B expression in the brain is highlighted.Expert opinion: Direct upregulation of the NR2B subunit expression can enhance synaptic plasticity and memory functions in a broad range of behavioral tasks in rodents. Other upregulation approaches, such as targeting the NR2B transporter or surface recycling pathway via cyclin-dependent kinase 5, are highly effective in improving memory functions. A dietary supplemental approach by optimally elevating the [Mg2+] in the brain is surprisingly effective in upregulating NR2B expression and improving memories in preclinical studies. MgT is currently under clinical trials.
机译：简介：与年龄有关的记忆丧失被认为是突触可塑性降低的结果，包括NMDA受体NR2亚基组成的变化。众所周知，内源性NR2B亚基会随着大脑年龄的增长而减少，而NR2B的转基因上调会增强突触的可塑性以及几种动物的学习记忆能力。越来越多的证据表明，通过饮食补充提高大脑中的镁含量，可以增强大脑中的NR2B，从而逆转记忆缺陷并增强认知能力。相关的内存丢失。通过口服摄取一种新型化合物L-苏氨酸镁（MgT）来增强大脑中NR2B表达的饮食方法被强调。专家意见：NR2B亚基表达的直接上调可以增强突触可塑性和广泛的记忆功能啮齿动物的行为任务范围。其他上调方法，例如通过细胞周期蛋白依赖性激酶5靶向NR2B转运蛋白或表面循环途径，在改善记忆功能方面非常有效。在临床前研究中，通过最佳地提高大脑中[Mg2 +]的饮食补充方法在上调NR2B表达和改善记忆方面出奇地有效。 MgT目前正在临床试验中。

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