摘要
大部分数据表明阿尔茨海默病包括CNS中淀粉样β-肽的累积和由Aβ清除缺陷引起的散发性AD。通过对机制相当多的关注,人们发现Aβ可能在脑和血液中运输,证据证明作为多药耐药(MDR)蛋白(ABCB1基因的产物)而著名的p-糖蛋白在Aβ通过血脑屏障(BBB)起作用。我们用两种方法测试了可能性:第一种,野生型和敲除MDA1A老鼠在静脉注射125I标记Aβ后60分钟,脑内匀浆组织进行TCA-沉淀物质的γ-计数和脑组织切片进行反射自显影。第二种,MDR1A敲除鼠与Tg2576APP转基因老鼠杂交,一种在脑内累积Aβ的常规方法;用酶联免疫吸附测定计算SDS和脑匀浆甲酸提取物的Aβ水平。两种方法都得出数据证明缺少MDR1A的老鼠Aβ的累积程度更高。这些发现证实了其它关于p-糖蛋白和Aβ通过血脑屏障消除的报告并对阿尔茨海默病遗传学,药理学和流行病学有重要意义。
关键词: 阿尔茨海默病,淀粉样β-肽,血脑屏障,血-脑脊液屏障,MDR1,P-糖蛋白,运输
Current Alzheimer Research
Title:A Role for P-Glycoprotein in Clearance of Alzheimer Amyloid β -Peptide from the Brain
Volume: 13 Issue: 6
Author(s): Wei Wang, Angela M. Bodles-Brakhop, Steven W. Barger
Affiliation:
关键词: 阿尔茨海默病,淀粉样β-肽,血脑屏障,血-脑脊液屏障,MDR1,P-糖蛋白,运输
摘要: Most data indicates that Alzheimer’s disease involves an accumulation of amyloid β - peptide (Aβ) in the CNS and that sporadic cases arise from a deficiency in Aβ clearance. Considerable attention has been given to mechanisms by which Aβ might be transported between the brain and blood, and evidence suggests that p-glycoprotein, also known as the multi-drug resistance (MDR) protein (product of the ABCB1 gene), plays a role in Aβ transport across the blood-brain barrier (BBB). We tested this possibility through two approaches: First, wild-type and MDR1A-knockout mice were compared after intravenous injection of [125I]-labeled Aβ; after 60 min, homogenates of brain parenchyma were subjected to γ-counting of TCA-precipitable material, and histological sections of brain were subjected to autoradiography. Second, MDR1Aknockout mice were crossed with Tg2576 APP transgenic mice, a line that routinely accumulates Aβ in the brain; SDS and formic acid extracts of brain homogenates were assessed for Aβ levels by ELISA. Each of these approaches yielded data indicating that Aβ accumulates to a greater degree in mice lacking MDR1A. These findings confirm other reports linking p-glycoprotein to Aβ clearance across the BBB and have important implications for Alzheimer’s disease genetics, pharmacology, and epidemiology.
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Cite this article as:
Wei Wang, Angela M. Bodles-Brakhop, Steven W. Barger , A Role for P-Glycoprotein in Clearance of Alzheimer Amyloid β -Peptide from the Brain, Current Alzheimer Research 2016; 13 (6) . https://dx.doi.org/10.2174/1567205013666160314151012
DOI https://dx.doi.org/10.2174/1567205013666160314151012 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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