Increased caveolin-1 expression in Alzheimer's disease brain
Increased caveolin-1 expression in Alzheimer's disease brain
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DOI：
10.1016/j.neurobiolaging.2003.07.004
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发表时间：
2004-07-01
影响因子：
4.2
通讯作者：
Poirier, J
中科院分区：
文献类型：
--
作者：
Gaudreault, SB;Dea, D;Poirier, J
越来越多的证据表明，胆固醇在阿尔茨海默病（AD）的病理生理中起着核心作用。小窝蛋白是一种参与细胞胆固醇运输的胆固醇结合膜蛋白。我们研究了尸检证实的AD和年龄匹配的对照组海马小窝蛋白的蛋白量变化。我们的研究结果表明，与对照大脑相比，阿尔茨海默病患者海马中的小窝蛋白水平和额叶皮层中的小窝蛋白mRNA水平上调了大约两倍。这些结果表明，小窝蛋白-1表达水平与脑细胞质膜胆固醇稳态失调之间存在关系。为了支持这一假设，在apoe缺陷（敲除）和衰老的野生型小鼠的海马组织中也观察到小窝蛋白水平的显著增加；两种与脑突触质膜中胆固醇跨双分子层分布改变有关的情况。这些结果表明，小窝蛋白的过度表达与脑细胞质膜中胆固醇分布的改变有关，并且与阿尔茨海默病中胆固醇稳态恶化的概念一致。(C) 2003 Elsevier Inc.版权所有。
Increasing evidence suggests that cholesterol plays a central role in the pathophysiology of Alzheimer's disease (AD). Caveolin is a cholesterol-binding membrane protein involved in cellular cholesterol transport. We investigated the changes in the protein amount of hippocampal caveolin of autopsy-confirmed AD and aged-matched control subjects. Our results demonstrate that caveolin protein levels in the hippocampus and caveolin mRNA in the frontal cortex are up-regulated in AD by approximately two-fold, compared to control brains. These results suggest a relationship between caveolin-1 expression levels and a dysregulation of cholesterol homeostasis at the plasma membrane of brain cells. In support of this hypothesis, a significant increase in caveolin protein levels has also been observed in hippocampal tissue from ApoE-deficient (knockout) and aged wild-type mice; two situations associated with modifications of transbilayer distribution of cholesterol in brain synaptic plasma membranes. These results indicate that caveolin over-expression is linked to alterations of cholesterol distribution in the plasma membrane of brain cells and are consistent with the notion of a deterioration of cholesterol homeostasis in AD. (C) 2003 Elsevier Inc. All rights reserved.