• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Neuron >The CAMKK2-AMPK Kinase Pathway Mediates the Synaptotoxic Effects of Aβ Oligomers through Tau Phosphorylation
【24h】

The CAMKK2-AMPK Kinase Pathway Mediates the Synaptotoxic Effects of Aβ Oligomers through Tau Phosphorylation

机译：CAMKK2-AMPK激酶途径通过Tau磷酸化介导Aβ低聚物的突触毒性作用。

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

Amyloid-β 1-42 (Aβ42) oligomers are synaptotoxic for excitatory cortical and hippocampal neurons and might play a role in early stages of Alzheimer's disease (AD) progression. Recent results suggested that Aβ42 oligomers trigger activation of AMP-activated kinase (AMPK), and its activation is increased in the brain of patients with AD. We show that increased intracellular calcium [Ca2+]i induced by NMDA receptor activation or membrane depolarization activates AMPK in a CAMKK2-dependent manner. CAMKK2 or AMPK overactivation is sufficient to induce dendritic spine loss. Conversely, inhibiting their activity protects hippocampal neurons against synaptotoxic effects of Aβ42 oligomers in vitro and against the loss of dendritic spines observed in the human APPSWE,IND-expressing transgenic mouse model in vivo. AMPK phosphorylates Tau on KxGS motif S262, and expression of Tau S262A inhibits the synaptotoxic effects of Aβ42 oligomers. Our results identify a CAMKK2-AMPK-Tau pathway as a critical mediator of the synaptotoxic effects of Aβ42 oligomers. Mairet-Coello et al. demonstrate that the CAMKK2-AMPK kinase pathway mediates the synaptotoxic effects of Ab42 oligomers in hippocampal neurons. These effects are mediated through the ability of AMPK to phosphorylate Tau on Serine 262.
机译：淀粉样β1-42（Aβ42）低聚物对兴奋性皮质和海马神经元具有突触毒性，并且可能在阿尔茨海默氏病（AD）的早期发展中发挥作用。最近的结果表明，Aβ42低聚物触发AMP激活激酶（AMPK）的激活，并且其激活在AD患者的大脑中增加。我们表明，增加的细胞内钙[Ca2 +] i由NMDA受体激活或膜去极化诱导以CAMKK2依赖性方式激活AMPK。 CAMKK2或AMPK过度激活足以引起树突状脊柱丢失。相反，抑制其活性可在体外保护海马神经元免受Aβ42寡聚物的突触毒性作用，并防止体内表达人APPSWE，IND的转基因小鼠模型中观察到的树突棘丧失。 AMPK使KxGS基序S262上的Tau磷酸化，Tau S262A的表达抑制Aβ42低聚物的突触毒性作用。我们的结果确定了CAMKK2-AMPK-Tau途径是Aβ42低聚物突触毒性作用的关键介质。 Mairet-Coello等。证明CAMKK2-AMPK激酶途径介导了海马神经元中Ab42寡聚物的突触毒性作用。这些作用是通过AMPK在丝氨酸262上磷酸化Tau的能力介导的。

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