Research Article

小檗碱通过激活APP / PS1转基因小鼠脑中的LKB1 / AMPK信号缓解淀粉样β发病机制

卷 19, 期 5, 2019

页: [342 - 348] 页: 7

弟呕挨: 10.2174/1566524019666190315164120

价格: $65

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摘要

背景:肝激酶B1(LKB1)/ 5''-腺苷单磷酸激活蛋白激酶(AMPK)信号传导是一种代谢检查点,在阿尔茨海默病(AD)的发病机制中起着神经保护作用。淀粉样蛋白-β(Aβ)充当AD的经典生物标志物。本研究的目的是探讨小檗碱(BBR)是否激活LKB1 / AMPK信号并改善Aβ病理。 方法:采用酶联免疫吸附试验和免疫组化法检测Aβ水平。通过蛋白质印迹测量以下生物标志物:磷酸化(p-)LKB1(Ser334和Thr189),p-AMPK(AMPKα和AMPKβ1),突触素,突触后密度蛋白95和p-cAMP-反应元件结合蛋白(p- CREB)。使用蛋白质印迹和免疫组织化学测定胶质原纤维酸性蛋白(GFAP)。 结果:BBR抑制APP / PS1小鼠脑内Aβ的表达。在BBR处理后,APP / PS1转基因小鼠的脑中p-LKB1(Ser334和Thr189)和p-AMPK(AMPKα和AMPKβ1)均有强烈的上调(P <0.01)。与模型小鼠相比,BBR促进AD脑中突触素,突触后密度蛋白95和p-CREB(Ser133)的表达。 结论:BBR通过激活APP / PS1转基因小鼠脑内LKB1 / AMPK信号通路,减轻Aβ发病机制,挽救突触损伤。

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