| 肥胖及2型糖尿病大鼠Alzheimer病样Tau蛋白过度磷酸化修饰及机制探讨 |
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| 引用本文： | 杨 雁,胡蜀红,张建华,张木勋,龚成新.肥胖及2型糖尿病大鼠Alzheimer病样Tau蛋白过度磷酸化修饰及机制探讨[J].生物化学与生物物理进展,2006,33(5):458-464. |
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| 作者姓名： | 杨 雁 胡蜀红 张建华 张木勋 龚成新 |
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| 作者单位： | 1. 华中科技大学同济医学院附属同济医院内分泌科,武汉,430030
2. Department of Neurochemistry,New York State Institute for Basic Research in Developmental Disabilities,New York,NY,10314,USA;华中科技大学同济医学院病理生理系,武汉,430030 |
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| 摘 要： | Tau蛋白异常过度磷酸化修饰在阿尔茨海默病(Alzheimerdisease,AD)发病机理中起非常重要的作用,而2型糖尿病是AD的风险因素之一.采用蛋白质印迹研究2型糖尿病及单纯肥胖大鼠脑中海马回tau蛋白磷酸化程度,发现在这两种大鼠模型中海马tau蛋白在多个位点上都呈现过度磷酸化状态.同时,胰岛素信号传导系统中的关键酶糖原合成激酶-3β(glycogensynthasekinase-3β,GSK-3β)活性在这两种大鼠模型的海马回中明显增高,经脑立体定位法向大鼠海马回注射GSK-3β抑制剂氯化锂(LiCl),可阻止2型糖尿病及肥胖大鼠模型中的GSK-3β激活,但仅阻止单纯肥胖大鼠海马回tau蛋白过度磷酸化.另外,海马神经细胞膜上胰岛素受体β亚基水平在两种实验模型中显著下降.研究结果表明,2型糖尿病及肥胖可能通过增高胰岛素抵抗,从而导致GSK-3β激活和tau蛋白的过度磷酸化来提高AD的发病风险.2型糖尿病脑中低下的葡萄糖代谢也可能在tau蛋白的过度磷酸化起一定作用.
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| 关 键 词： | 胰岛素抵抗 阿尔茨海默病 Tau蛋白 糖原合成酶激酶-3β 过度磷酸化 |
| 收稿时间： | 2005-11-01 |
| 修稿时间： | 2005-11-012005-12-29 |
Alzheimer-like Hyperphosphorylation of Tau in Brains of Rats With Obesity and Type 2 Diabetes |
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| YANG Yan,HU Shu-Hong,ZHANG Jian-Hu,ZHANG Mu-Xun and GONG Cheng-Xin.Alzheimer-like Hyperphosphorylation of Tau in Brains of Rats With Obesity and Type 2 Diabetes[J].Progress In Biochemistry and Biophysics,2006,33(5):458-464. |
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| Authors: | YANG Yan HU Shu-Hong ZHANG Jian-Hu ZHANG Mu-Xun and GONG Cheng-Xin |
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| Institution: | Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York, NY 10314, USA;Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China |
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