阿尔次海默病tau蛋白异常修饰与其功能的关系

The Relationship Between Abnormal Modification of tau and Its Biological Activity in Alzheimer Disease.

阿尔次海默病易溶型胞浆ｔａｕ和难溶型双螺旋丝中的ｔａｕ均被异常磷酸化和异常糖基化修饰．异常修饰的ｔａｕ丧失其促微管组装活性，用不同蛋白磷酸酯酶对难溶型双螺旋丝中的ｔａｕ去磷酸化处理后可不同程度恢复其促微管组装生物学活性．单纯去糖基化处理只在很小限度恢复ｔａｕ的功能，但去糖基化预处理可增强去磷酸化对ｔａｕ上述活性的恢复．提示：ａｔａｕ的异常磷酸化是导致其功能活性丧失的直接因素，而糖基化修饰可能通过对其结构的影响而间接对ｔａｕ功能活性发挥作用；ｂ蛋白磷酸酯酶可部分抑制和逆转阿尔次海默病的脑病理损伤．

Both soluble abnormally phosphorylated tau and tau in paired helical filaments are abnormally glycosylated . Abnormally modified tau is incompetent in promoting the assembly of microtubules. Dephosphorylation of insoluble tau with various phosphatases restores differentially the biologic activity of tau in promoting the assembly of microtubules. Deglycosylation of tau enhances the above mentioned activity caused by dephosphorylation although deglycosylation alone has no significant effect on restoring the biological activity of tau. These data suggest that abnormal phosphorylation of tau might be the direct factor for its deficient function whereas glycosylation might be an indirect one by affecting the structure of tau; that protein phosphatases might arrest and reverse the lessions in Alzheimer brain.