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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

金雀异黄素通过抑制CIP2A降低APP / tau磷酸化并改善Aβ过量生产

卷 16, 期 8, 2019

页: [732 - 740] 页: 9

弟呕挨: 10.2174/1567205016666190830113420

价格: $65

摘要

背景：PP2A癌性抑制剂（CIP2A）的上调通过抑制AD脑中的PP2A在tau / APP的疾病相关磷酸化和tau病理学/Aβ的过度生产中起重要作用。在实验性癌症治疗研究中，染料木黄酮已显示出有效降低CIP2A的作用。金雀异黄素是否可以通过靶向CIP2A改善AD病理，尚需进一步研究。 方法：探讨了染料木黄酮对AD细胞模型中tau / APP磷酸化和Aβ过度产生的抑制作用。将HEK293-T细胞与CIP2A和APP质粒，或CIP2A和tau质粒共转染，并在0、30、60或120μMGenistein中孵育48 h，测量细胞活力和PP2A活性。收集用Genistein在30μM下处理过表达CIP2A / APP的HEK293-T细胞48 h，并裂解以进行CIP2A，PP2Ac，APP-T668，总APP，PS1，BACE1，sAPPα和sAPPβ的Western印迹检测。通过ELISA测量细胞上清液中的Aβ40和Aβ42水平，细胞裂解物的可溶级分（RIPA）和不溶级分（甲酸可溶）。用Genistein在30μM下处理48h的CIP2A / tau过表达的HEK293-T细胞，用于CIP2A，PP2Ac，tau-S396，tau-S404和总tau蛋白的蛋白质印迹检测。 结果：染料木黄酮有效降低了CIP2A的表达，并恢复了CIP2A / APP，CIP2A / tau共表达细胞中的PP2A活性。金雀异黄素减少了T668位点的APP磷酸化并抑制了Aβ的产生。同时，金雀异黄素通过抑制CIP2A对PP2A的抑制作用来改善tau过度磷酸化。 结论：CIP2A是Genistein在AD治疗中的靶标。金雀异黄素通过抑制CIP2A对PP2A的作用来减少APP / tau的过度磷酸化和Aβ的产生。

关键词: CIP2A，染料木黄酮，tau，APP β-切割，阿尔茨海默氏病，神经原纤维。

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