葡萄糖转运体减少与阿尔茨海默病中tau蛋白的异常过度磷酸化相关。
Decreased glucose transporters correlate to abnormal hyperphosphorylation of tau in Alzheimer disease.
作者信息
Liu Ying, Liu Fei, Iqbal Khalid, Grundke-Iqbal Inge, Gong Cheng-Xin
机构信息
Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA.
出版信息
FEBS Lett. 2008 Jan 23;582(2):359-64. doi: 10.1016/j.febslet.2007.12.035. Epub 2008 Jan 2.
Abstract
Brain glucose uptake/metabolism 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.
摘要
阿尔茨海默病（AD）患者大脑中的葡萄糖摄取/代谢受损。在此，我们报告称，负责将葡萄糖摄取到神经元中的两种主要脑葡萄糖转运蛋白（GLUT1和GLUT3）的水平在AD大脑中降低。这种降低与O-连接N-乙酰葡糖胺化的减少、tau蛋白的过度磷酸化以及人类大脑中神经原纤维缠结的密度相关。我们还发现，在AD大脑中，缺氧诱导因子1（GLUT1和GLUT3的主要调节因子）下调。这些研究提供了一种可能的机制，通过该机制，GLUT1和GLUT3缺乏可能导致大脑葡萄糖摄取/代谢受损，并通过下调AD中O-连接N-乙酰葡糖胺化和tau蛋白过度磷酸化而促进神经退行性变。
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