Luo Yougen, Zhou Xinwen, Yang Xifei, Wang Jianzhi
Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Neuroreport. 2007 Dec 3;18(18):2005-8. doi: 10.1097/WNR.0b013e3282f29100.
Epidemiological and clinical data suggest that homocysteine (Hcy) may increase the risk of Alzheimer's disease, but the underlying mechanisms are elusive. To investigate the effect of Hcy on phosphorylation of tau, we injected Hcy into the lateral cerebral ventricle of rats. We found that level of the hyperphosphorylated tau at PHF-1 (Ser396/404) and tau-1 (Ser198/199/202) epitopes was elevated prominently at 6, 9, and 12 h after the injection, and it was recovered to normal at 24 h. Simultaneously, the level of protein phosphatase-2A catalytic subunit (PP-2Ac) was reduced markedly as compared with control. These results imply that Hcy may induce hyperphosphorylation of tau with PP-2Ac involved mechanism.
流行病学和临床数据表明，同型半胱氨酸（Hcy）可能会增加患阿尔茨海默病的风险，但其潜在机制尚不清楚。为了研究Hcy对tau蛋白磷酸化的影响，我们将Hcy注入大鼠侧脑室。我们发现，注射后6小时、9小时和12小时，PHF-1（Ser396/404）和tau-1（Ser198/199/202）表位的过度磷酸化tau蛋白水平显著升高，并在24小时恢复正常。同时，与对照组相比，蛋白磷酸酶2A催化亚基（PP-2Ac）水平明显降低。这些结果表明，Hcy可能通过PP-2Ac参与的机制诱导tau蛋白过度磷酸化。
