Brain glucose transporters, O-GlcNAcylation and phosphorylation of tau in diabetes and Alzheimer's disease.
Brain glucose transporters, O-GlcNAcylation and phosphorylation of tau in diabetes and Alzheimer's disease.
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DOI：
10.1111/j.1471-4159.2009.06320.x
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发表时间：
2009-10
影响因子：
4.7
通讯作者：
Gong CX
中科院分区：
文献类型：
--
作者：
Liu Y;Liu F;Grundke-Iqbal I;Iqbal K;Gong CX
2型糖尿病（T2 DM）增加了阿尔茨海默病（AD）的风险，但其潜在机制尚不清楚。在这项研究中，我们确定了7名对照者、11名T2 DM受试者、10名AD受试者和8名同时患有T2 DM和AD的受试者的额叶皮质的死后脑组织中主要脑葡萄糖转运蛋白（GLUT）、O-GlcNAc化和tau磷酸化的水平。我们发现，神经元GLUT 3在T2 DM脑中的降低程度大于AD脑。如在AD脑中所见，T2 DM脑中总体蛋白和tau的O-GlcNAc化水平也降低。在T2 DM脑中，一些AD异常过度磷酸化位点的tau磷酸化增加。这些结果表明，T2 DM可能通过损害脑葡萄糖摄取/代谢，从而下调O-GlcNAc酰化（促进tau异常过度磷酸化），导致AD风险增加。
Type 2 diabetes mellitus (T2DM) increases the risk for Alzheimer disease (AD), but the underlying mechanism is unknown. In this study, we determined the levels of major brain glucose transporters (GLUT), O-GlcNAcylation and phosphorylation of tau in the postmortem brain tissue from frontal cortices of 7 controls, 11 T2DM subjects, 10 AD subjects and 8 additional subjects who had both T2DM and AD. We found that the neuronal GLUT3 was decreased to a bigger extent in T2DM brain than in AD brain. The O-GlcNAcylation levels of global proteins and of tau were also decreased in T2DM brain as seen in AD brain. Phosphorylation of tau at some of the AD abnormal hyperphosphorylation sites was increased in T2DM brain. These results suggest that T2DM may contribute to the increased risk for AD by impairing brain glucose uptake/metabolism and, consequently, down-regulation of O-GlcNAcylation, which facilitates abnormal hyperphosphorylation of tau.
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影响因子：
4.7
作者：
Haase, C;Stieler, JT;Holzer, M
通讯作者：
Holzer, M
影响因子：
3.4
作者：
Liu, Fei;Li, Bin;Gong, Cheng-Xin
通讯作者：
Gong, Cheng-Xin
影响因子：
3.5
作者：
Liu, Ying;Liu, Fei;Gong, Cheng-Xin
通讯作者：
Gong, Cheng-Xin
影响因子：
4.3
作者：
Cechetto, David F;Hachinski, Vladimir;Whitehead, Shawn N
通讯作者：
Whitehead, Shawn N
影响因子：
2.9
作者：
BENSADOUN, A;WEINSTEIN, D
通讯作者：
WEINSTEIN, D