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标题：Uptake of Aβ by OATPs might be a new pathophysiological mechanism of Alzheimer disease
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作者：Jinhua Wen ; Menghua Zhao ; Wenxiong Sun 等
期刊名称：BMC Neuroscience
印刷版ISSN：1471-2202
电子版ISSN：1471-2202
出版年度：2021
卷号：22
DOI：10.1186/s12868-021-00658-9
语种：English
出版社：BioMed Central
摘要：Background The accumulation of neurotoxic amyloid-beta (Aβ) in the brain is a characteristic of Alzheimer's disease (AD), at the same time, it is possible alterations of liver function could affect brain Aβ levels through changes in blood Aβ concentration. Over the last decade, a number of reports have shown that P-glycoprotein (encoded by ABC1B1) actively mediates the efflux transport of Aβ peptides. However, the mechanism by which Aβ peptides enter the cells is not clear. In the preliminary study, we found that the protein expression of organic anion transporting Polypeptide 1a4 (OATP1B1) in the liver tissue of mice with AD was significantly higher than that in the normal mice. In contrast, the protein expression of Oatp1a4 in the brain significantly decreased in mice with AD. OATP1B1, an important drug transporter might be related to the pathophysiology of AD. Results In this study, we established an OATP1B1-GFP-HEK293T cell model to confirm the OATP1B1 mediated transport of Aβ 1-42. Compared to the control group of GFP-HEK293Tcells, the uptake of Aβ 1-42 protein in the OATP1B1-GFP-HEK293T group increased significantly with the increase in concentration of Aβ 1-42, and also increased significantly with an increase in the duration of incubation. Similar results were observed in the flow cytometry experiment, and the uptake of Aβ 1-42in HEK293T-OATP1B1 cells was almost twice that in the control group. These results indicate that OATPs may act as an important “carrier” for the transport of Aβ1-42 from the blood to the tissues, including liver and brain. Conclusions This is a novel and interesting finding and OATP1B1 can be investigated as a new treatment target for AD. Supplementary Information The online version contains supplementary material available at 10.1186/s12868-021-00658-9.
关键词：OATPs; Alzheimer disease; Beta-amyloid