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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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Research Article

阳离子镓酞菁抑制淀粉样β肽原纤维形成。

卷 17, 期 7, 2020

页: [589 - 600] 页: 12

弟呕挨: 10.2174/1567205017666201008112002

价格: $65

摘要

背景：淀粉样β（Aβ）肽沉积被认为是阿尔茨海默氏病（AD）的主要原因。以前，我们已经表明，含锌的中性酞菁（Zn-Pc）会抑制Aβ原纤维的形成。 目的：本研究的目的是研究含阳离子的镓（Pc）（GaCl-Pc）对Aβ原纤维形成过程的影响。 方法与结果：通过在原纤维形成缓冲液中孵育合成的Aβ肽诱导Aβ纤维形成，并通过ThT荧光分析法评估原纤维的含量。 GaCl-Pc剂量依赖性地抑制Aβ1-40和Aβ1-42的原纤维形成。它主要抑制Aβ1-42原纤维形成动力学的延伸阶段，而不抑制滞后阶段。蛋白质印迹结果表明，它不会抑制其低聚过程，反而会增加它。另外，GaCl-Pc在体外条件下使预先形成的Aβ1-42原纤维不稳定，并在APP转基因AD模型小鼠（J20株）的脑切片培养物中降低了Aβ水平。近红外扫描结果表明，GaCl-Pc具有与Aβ1-42结合的能力。 MTT分析表明，GaCl-Pc对培养的神经元细胞系（A1）没有毒性，而是对Aβ诱导的毒性具有保护作用。此外，它剂量依赖性地降低了A1培养物中Aβ诱导的活性氧的水平。 结论：因此，我们的结果证明GaCl-Pc减少了Aβ聚集并破坏了预形成的原纤维。由于阳离子分子表现出更好的穿过血脑屏障的能力，因此阳离子GaCl-Pc对于AD的治疗可能很重要。

关键词: 阿尔茨海默氏病，淀粉样β肽，原纤维形成，阳离子酞菁，神经元培养，细胞毒性。

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