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当代阿耳茨海默病研究

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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General Research Article

黄腐酚及其衍生物对阿尔茨海默氏病的淀粉样β聚集的抑制和神经保护作用。

卷 16, 期 9, 2019

页: [836 - 842] 页: 7

弟呕挨: 10.2174/1567205016666190827123222

价格: $65

摘要

背景：据报道黄腐酚具有通过激活Nrf2-ARE信号通路而具有细胞保护作用；并且它具有清除自由基的能力，表明其具有预防神经变性的潜力。然而，黄腐酚的生物相容性和血脑屏障不可渗透性阻碍了其在体内治疗阿尔茨海默氏病（AD）的潜力。 目的：我们设计并制备了一系列黄腐酚衍生物，以增强所需的物理，生物学和药理特性，尤其是用于干预AD的血脑屏障通透性。 方法：我们设计并合成了一系列新的9种黄腐酚衍生物。探索了它们对β-淀粉样蛋白（1-42），Aβ1-42的抑制作用，低聚和原纤维化以及对β-淀粉样蛋白诱导的毒性的神经保护作用。 结果：在9种黄腐酚衍生物中，一些对Aβ1-42的低聚和原纤化具有中等至高的抑制作用。通过减少由淀粉样蛋白β诱导的ROS生成和钙上载，它们对SH-SY5Y细胞具有生物相容性和神经保护作用。重要的是，发现其中两个衍生物是血脑屏障可渗透的，显示出有希望的AD治疗潜力。 结论：已经确定了两种衍生物具有生物相容性，无毒，对Aβ诱导的毒性具有神经保护作用，并且具有血脑屏障可渗透性，突出了它们作为AD候选药物在未来临床应用中的潜力。

关键词: 黄腐酚的衍生物，具有神经保护作用，抑制淀粉样蛋白聚集，可渗透血脑屏障。

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