Decreased glucose transporters correlate to abnormal hyperphosphorylation of tau in Alzheimer disease
Decreased glucose transporters correlate to abnormal hyperphosphorylation of tau in Alzheimer disease
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DOI：
10.1016/j.febslet.2007.12.035
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发表时间：
2008-01-01
期刊：
影响因子：
3.5
通讯作者：
Gong, Cheng-Xin
中科院分区：
文献类型：
--
作者：
Liu, Ying;Liu, Fei;Gong, Cheng-Xin
阿尔茨海默病（AD）患者脑葡萄糖摄取代谢受损。在这里，我们报告了AD大脑中负责葡萄糖摄取到神经元的两种主要脑葡萄糖转运蛋白（GLUT1和GLUT3）的水平下降。这种减少与o - glcn酰化的减少、tau蛋白的过度磷酸化以及人脑中神经原纤维缠结的密度有关。我们还发现缺氧诱导因子1 （GLUT1和GLUT3的主要调节因子）在AD大脑中下调。这些研究提供了一种可能的机制，通过下调AD患者的o - glcn酰化和tau蛋白的过度磷酸化，GLUT1和GLUT3缺乏可能导致脑葡萄糖摄取/代谢受损，并导致神经退行性变。(C) 2007年欧洲生化学会联合会。Elsevier B.V.版权所有。
Brain glucose uptakelmetabolism is impaired in Alzheimer disease (AD). Here, we report that levels of the two major brain glucose transporters (GLUT1 and GLUT3) responsible for glucose uptake into neurons were decreased in AD brain. This decrease correlated to the decrease in O-GlcNAcylation, to the hyperphosphorylation of tau, and to the density of neurofibrillary tangles in human brains. We also found down-regulation of hypoxia-inducible factor 1, a major regulator of GLUT1 and GLUT3, in AD brain. These studies provide a possible mechanism by which GLUT1 and GLUT3 deficiency could cause impaired brain glucose uptake/metabolism and contribute to neurodegeneration via down-regulation of O-GlcNAcylation and hyperphosphorylation of tau in AD. (C) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.