Muñoz-Montaño J R, Moreno F J, Avila J, Diaz-Nido J
Centro de Biología Molecular Severo Ochoa, Facultad de Ciencias, Universidad Autónoma de Madrid, Spain.
FEBS Lett. 1997 Jul 14;411(2-3):183-8. doi: 10.1016/s0014-5793(97)00688-1.
In Alzheimer's disease, tau protein becomes hyperphosporylated, which can contribute to neuronal degeneration. However, the implicated protein kinases are still unknown. Now we report that lithium (an inhibitor of glycogen synthase kinase-3) causes tau dephosphorylation at the sites recognized by antibodies Tau-1 and PHF-1 both in cultured neurons and in vivo in rat brain. This is consistent with a major role for glycogen synthase kinase-3 in modifying proline-directed sites on tau protein within living neurons under physiological conditions. Lithium also blocks the Alzheimer's disease-like proline-directed hyperphosphorylation of tau protein which is observed in neurons treated with a phosphatase inhibitor. These data raise the possibility of using lithium to prevent tau hyperphosphorylation in Alzheimer's disease.
在阿尔茨海默病中，tau蛋白发生过度磷酸化，这可能导致神经元变性。然而，与之相关的蛋白激酶仍不清楚。现在我们报告，锂（糖原合酶激酶-3的抑制剂）在培养的神经元和大鼠脑内均可使tau蛋白在抗体Tau-1和PHF-1识别的位点去磷酸化。这与糖原合酶激酶-3在生理条件下修饰活神经元内tau蛋白上脯氨酸定向位点的主要作用是一致的。锂还可阻断在用磷酸酶抑制剂处理的神经元中观察到的类似阿尔茨海默病的tau蛋白脯氨酸定向过度磷酸化。这些数据增加了使用锂来预防阿尔茨海默病中tau蛋白过度磷酸化的可能性。
