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当代阿耳茨海默病研究

Editor-in-Chief

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

Research Article

通过调节BACE1活性导致Salvianolic acid B产生淀粉样蛋白β的减少

卷 14, 期 11, 2017

页: [1229 - 1237] 页: 9

弟呕挨: 10.2174/1567205014666170417103003

价格: $65

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摘要

目的:通过β-分泌酶(β位点APP切割酶或BACE1)和γ-分泌酶对全长淀粉样蛋白前体蛋白(FL-APP)蛋白水解加工后淀粉样蛋白β(Aβ)肽的产生和积累是主要的阿尔茨海默氏病(AD)的因果因素。因此,抑制Aβ生成中限速酶BACE1是治疗AD的有吸引力的治疗方法。最近的研究表明,丹参酸B(Sal B)是从中国通常用于治疗心血管,脑血管和肝脏疾病的中草药丹参中分离出来的。 方法:在这项研究中,我们发现Sal B作为BACE1调节剂,并降低了两种不同的瑞典APP(SwedAPP)突变细胞系中分泌的Aβ的水平。使用表达SwedAPP的N2a-小鼠和H4-人神经胶质瘤细胞系,证实Sal B显着和剂量依赖性地降低细胞外Aβ的产生,可溶性APPβ(由BACE1切割的APP的副产物)和细胞内C-末端来自APP的片段β,不影响α-分泌酶和γ-分泌酶活性以及FL-APP的水平。此外,使用蛋白质对接,我们确定了Sal B对BACE1对接的潜在构象,并揭示了Sal B与BACE1催化中心的相互作用。 结果:对接提供了实验结果的可行解释,特别是在Sal B的作用的分子基础上。我们的研究结果表明,Sal B是一种BACE1抑制剂,因此是治疗AD的有希望的候选者

关键词: Aβ生成,BACE-1,对接,Salvianolic acid B,可溶性淀粉样蛋白前体蛋白β,中药。

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