• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Glutamate receptors in preclinical research on Alzheimer's disease: Update on recent advances
【24h】

Glutamate receptors in preclinical research on Alzheimer's disease: Update on recent advances

机译：谷氨酸受体在阿尔茨海默病的临床前研究中：最近进步的更新

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The cognitive and related symptoms of Alzheimer's disease are mainly attributable to synaptic failure. Here we review recent research on how the Alzheimer's disease amyloid ?-protein (A?) affects glutamate receptors and fast excitatory synaptic transmission and plasticity of that transmission. l-glutamate, the main excitatory neurotransmitter in the brain, has long been implicated in causing NMDA receptor-mediated excitotoxicity leading to neurodegeneration in the late stages of the disease. However there is now extensive evidence that soluble A? oligomers disrupt synaptic transmission and especially synaptic plasticity via non-excitotoxic glutamatergic mechanisms. New data highlight the relatively selective involvement of certain glutamate receptor subtypes including GluN2B (NR2B) subunit-containing NMDA receptors and mGlu5 receptors. A? exerts direct and indirect effects on synaptic plasticity-related glutamate receptor signaling and trafficking between different neuronal compartments. For example, A?-induced ectopic NMDA and mGlu receptor-mediated signaling coupled with caspase-3 activation may cause inhibition of long-term potentiation and facilitation of long-term depression. Intriguingly, some of the disruptive synaptic actions of A? have been found to be dependent on endogenous tau located in dendrites or spines. Given the role of glutamatergic transmission in regulating A? production and release, future therapies targeting glutamate offer the opportunity to remedy both mis-processing of A? and cellular mechanisms of synaptic failure in early AD.
机译：阿尔茨海默病的认知和相关症状主要归因于突触衰竭。在这里，我们审查了最近对阿尔茨海默病淀粉样蛋白的蛋白蛋白蛋白β-蛋白质（a≤）的研究影响了谷氨酸受体和快速兴奋性突触传递和该传动的可塑性。 L-谷氨酸大脑中的主要兴奋性神经递质，长期以来一直涉及导致NMDA受体介导的兴奋毒性导致疾病的晚期神经变性。然而，现在有广泛的证据可以解决问题？低聚物通过非吞噬毒素谷氨酸机构扰乱突触透射和尤其是突触可塑性。新数据突出了某些谷氨酸受体亚型的相对选择性涉及，包括GLUN2B（NR2B）亚单位的NMDA受体和MGLU5受体。一种？对突触塑性相关的谷氨酸受体信号传导和不同神经元隔室之间的直接和间接影响。例如，诱导的异位NMDA和MGLU受体介导的信号传导与Caspase-3激活相结合，可能导致长期增强和长期抑郁促进的抑制。有趣的是，一些破坏性突触作用是什么？已被发现依赖于位于树突或刺的内源性Tau。鉴于谷氨酸胶传输在调节a中的作用？生产和释放，未来靶向谷氨酸的疗法提供了纠正既有误解的机会？早期广告突触衰竭的细胞机制。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号