摘要
背景:APOE4等位基因是阿尔兹海默病(AD)中最强的遗传风险因素。它与淀粉样蛋白-β (Aβ)在脑内的积累相关,这是通过淀粉样蛋白前体裂解的β前区蛋白所产生。换言之,AβPP也是通过α –secretases想A去整合素和金属蛋白酶结构域蛋白10 (ADAM10)裂解产生。 目的:尽管一些研究证明了apoE on β- 和γ-secretase的影响,但是apoE和α-secretases之间的相互作用还没有完全被检测。我们调查了每种ADAM10在人类体外皮质样品中的apoE同工物的影响。 方法:ADAM10的活动和动力学在无细胞文章的评估和ADAM10的生物活动在7WCHO细胞中进一步调查酶联免疫吸附法检测野生型AβPP, 最终,ADAM10表达和活动在可溶解性成分控制阿尔兹海默病人类同工物样品中通过ELISA被观察检测。结果:在一个无细胞试验中,发现ADAM10的活动较在apoE2中显著低于在qpoE4样品中。7WCHO细胞过表达宽度类型AβPP的暴露较apoE isoforms 相比apoE4宣称减少sAβPPα类型。我们检测出APOE和AD在ADAM10活动中的变化和在人类大脑同工物中可溶解的大脑部分中的表达。 结论:总的来说,我们的数据表明基于apoE形式在ADAM10功能和ABPP进程中的影响,这种进程可以描述在AD患者携带APOE4等位基因的大脑淀粉样蛋白水平升高。
关键词: 阿尔兹海默病,ADAM10,α-分泌酶、载脂蛋白E,APOE,淀粉样蛋白
Current Alzheimer Research
Title:Apolipoprotein E-mediated Modulation of ADAM10 in Alzheimer's Disease
Volume: 14 Issue: 6
关键词: 阿尔兹海默病,ADAM10,α-分泌酶、载脂蛋白E,APOE,淀粉样蛋白
摘要: Background: The APOE4 allele is the strongest genetic risk factor for Alzheimer's disease (AD). It has been associated with an accumulation of amyloid-β (Aβ) in the brain, which is produced through the sequential cleavage of the amyloid-β precursor protein (AβPP) by β - and γ-secretases. Alternatively, AβPP is also cleaved by α -secretases such as A Disintegrin and Metalloproteinase Domain-containing Protein 10 (ADAM10).
Objective: While several studies have investigated the impact of apoE on β- and γ-secretase, interactions between apoE and α-secretases have not been fully examined. We investigated the effect of each apoE isoform on ADAM10 in vitro and in human cortex samples. Method: ADAM10 activity and kinetics was assessed in cell-free assays and the biological activity of ADAM10 further investigated in 7WCHO cells over-expressing wild type AβPP through ELISA. Finally, ADAM10 expression and activity was observed in the soluble fraction of both control and Alzheimer's Disease human cortex samples through ELISA. Results: In a cell free assay, ADAM10 activity was found to be significantly lower in apoE4 samples compared to apoE2. 7WCHO cells over expressing wild type AβPP exposed to apoE4 demonstrated reduced formation of sAβPPα compared to other apoE isoforms. We also identified APOE and AD dependent changes in ADAM10 activity and expression in the soluble brain fraction of human brain cortex. Conclusion: Overall, our data demonstrates an apoE isoform-dependent effect on ADAM10 function and AβPP processing which may describe the elevated amyloid levels in the brains of AD subjects carrying the APOE4 allele.Export Options
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Cite this article as:
Apolipoprotein E-mediated Modulation of ADAM10 in Alzheimer's Disease, Current Alzheimer Research 2017; 14 (6) . https://dx.doi.org/10.2174/1567205014666170203093219
DOI https://dx.doi.org/10.2174/1567205014666170203093219 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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