文献类型：期刊文献

英文题名：The characteristics of astrocyte on Aβ clearance altered in Alzheimer's disease were reversed by anti-inflammatory agent (+)-2-(1-hydroxyl-4-oxocyclohexyl) ethyl caffeate

作者：Liu, Rui-Xuan[1];Huang, Cui[1];Bennett, David A.[2,3];Li, Honglin[1];Wang, Rui[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Wuhan Univ, Sch Publ Hlth, Dept Nutr & Food Hlth, Wuhan, Peoples R China;[3]Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA

年份：2016

卷号：8

期号：10

起止页码：4082

外文期刊名：AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000387650100007)】；

基金：This project was supported by the grants from National Natural Science Foundation of China 81072627 and 81230090; the 111 Project (Grant No. B07023) from Ministry of Education; Key project from Shanghai Science and Technology Committee (12431900901). The human samples used in this study are from NIH grants to David Bennett (P30AG10161, R01AG15819). We are grateful to Dr. Wei Huang (Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin) for the technical support and valuable comments on the manuscript writing.

语种：英文

外文关键词：Alzheimer's disease; astrocyte; A beta clearance; neprilysin; inflammation; HOEC

摘要：Astrocytes are closely related to the amyloid-beta (A beta) deposition in the brain and play crucial roles in Alzheimer's disease (AD) pathology. Meanwhile, inflammation in the CNS has been increasingly demonstrated as a prominent hallmark in AD. Our data from animal models and subjects with Alzheimer's disease (AD) showed GFAP immunoreactivity altered in different stage of AD and had a positive correlation with neprilysin (NEP), suggesting astrocytes might take a protective role in pathogenetic course of AD. Here, we investigate the role of astrocyte in the mechanism of A beta removal. ELISA and western blotting were performed to determine the ability of astrocyte to clear A beta(1-42). In this study, we demonstrated that cultured astrocytes removed extracellular oligomeric A beta. However, cultured astrocytes from an AD mouse model showed less capacity to clear extracellular A beta(42) but with hyper-expression of NEP protein than normal astrocytes. In addition, LPS-induced inflammation rather than continuous A beta stimuli inhibited the capacity of A beta clearance by astrocytes indicating that inflammation possibly contributed to astrocytic dysfunction. Lastly, HOEC which exhibited anti-inflammatory effects restored the capacity of injured or aged astrocytes to clear A beta. In conclusion, astrocytes have been shown to exert a direct role in A beta clearance and undergo functional impair associated with inflammation in the pathogenesis of AD. Therefore, anti-inflammatory treatments aimed at restoring astrocyte functions may represent an appropriate approach to treat AD.