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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

褪黑素通过调节淀粉样前体蛋白-结合蛋白1途径，防止了Aβ42-暴露的SH-SY5Y神经母细胞瘤细胞中的类泛素化功能障碍

卷 17, 期 5, 2020

页: [446 - 459] 页: 14

弟呕挨: 10.2174/1567205017666200624201356

价格: $65

摘要

背景:淀粉样前体蛋白(APP)结合蛋白1 (APP-BP1)是许多关键信号通路的重要调控因子，主要作为一种支架蛋白，增强分子间相互作用，促进催化反应。APP-BP1与APP的相互作用在细胞周期调控中发挥作用，这决定了阿尔茨海默病(AD)细胞周期调控缺失的机制。相比之下，泛素化修饰，一种由泛素样蛋白神经前体细胞表达的发育下调蛋白8 (NEDD8)偶联介导的翻译后修饰，被一种由APP-BP1和NEDD8激活酶E1催化亚基(Uba3)组成的异源二聚体激活。NEDD8控制着重要的生物事件，和APP-BP1一样，它的水平在AD中被解除管制。 目的:本文研究了褪黑素在生理和病理条件下调节APP-BP1通路的作用，以了解其潜在机制。 方法: 人类SH-SY5Y神经母细胞瘤细胞用不同浓度的Aβ-42处理后可产生类似AD的神经毒性。 结果:该结果首次证明了褪黑素可以阻止由Aβ-42诱导的APP-BP1蛋白表达的增强和NEDD8细胞定位的改变。此外，我们还利用MLN4924 (APP-BP1通路阻断剂)验证了APP-BP1通路下游效应级联的成分，包括tau、APP -裂解分泌素、β-连环蛋白和p53。 结论: 褪黑素可调控与APP-BP1通路相关分子信号的相互作用，可能阻断疾病发生过程中的致病机制，为预防AD提供有利的治疗策略。

关键词: 阿兹海默病，褪黑素，淀粉样前体蛋白-结合蛋白1，类泛素化修饰，淀粉样蛋白，tau，分泌素，β-连环蛋白。

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