期刊
MOLECULAR ASPECTS OF MEDICINE
卷 30, 期 3, 页码 171-179出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.mam.2009.02.001
关键词
Blood-brain barrier; 24S-Hydroxycholesterol; 27-Hydroxycholesterol; beta-Amyloid; Activity regulated cytoskeleton-associated protein; CYP27; CYP46
资金
- Swedish Science Council
- Swedish Brain Power
In contrast to their parent molecule cholesterol, two of its side-chain oxidized metabolites are able to cross the blood-brain barrier. There is a concentration-driven flux of 24S-hydroxycholesterol (245-OHC) from the brain into the circulation, which is of major importance for elimination of excess cholesterol from the brain. The opposite flux of 27-hydroxycholesterol (27-OHC) from the circulation into the brain may regulate a number of key enzymes within the brain. In vitro experiments suggest that the balance between the levels of these two molecules may be of importance for the generation of beta-amyloid peptides. In primary cultures of rat hippocampal cells 27-OHC is able to suppress expression of the activity regulated cytoskeleton-associated protein (Arc), a protein important in memory consolidation which is reduced in patients with Alzheimer's disease (AD). In the present work we explore the possibility that the flux of 27-OHC from the circulation into the brain represents the missing link between AD and hypercholesterolemia, and discuss the possibility that modification of this flux may be a therapeutic strategy. Lastly, we discuss the use of oxysterols as diagnostic markets in neurodegenerative disease. (C) 2009 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据