Pei J J, Tanaka T, Tung Y C, Braak E, Iqbal K, Grundke-Iqbal I
NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
J Neuropathol Exp Neurol. 1997 Jan;56(1):70-8. doi: 10.1097/00005072-199701000-00007.
A number of studies have implicated a proline-directed protein kinase, glycogen synthase kinase-3 (GSK-3) in the hyperphosphorylation of tau in Alzheimer's disease (AD). Toward understanding the role of GSK-3 in the abnormal hyperphosphorylation of tau in AD we have found that GSK-3 is prominently present in neuronal cell bodies and their processes and co-localizes with neurofibrillary changes in AD brain. Furthermore, the levels of GSK-3 as determined by indirect ELISA are approximately 50% increased in the postsynaptosomal supernatant from AD brains as compared to the controls. However, no increase in GSK-3 enzyme activity was detected. In AD brain, with its reduced phosphatase activity, even normal levels of GSK-3 activity might be sufficient for the hyperphosphorylation of tau.
多项研究表明，一种脯氨酸定向蛋白激酶——糖原合酶激酶-3（GSK-3）与阿尔茨海默病（AD）中tau蛋白的过度磷酸化有关。为了了解GSK-3在AD中tau蛋白异常过度磷酸化中的作用，我们发现GSK-3在神经元细胞体及其突起中显著存在，并且与AD脑内的神经原纤维变化共定位。此外，通过间接酶联免疫吸附测定法（ELISA）测定，与对照组相比，AD脑突触后体上清液中GSK-3的水平约增加了50%。然而，未检测到GSK-3酶活性的增加。在AD脑中，由于其磷酸酶活性降低，即使是正常水平的GSK-3活性可能也足以使tau蛋白过度磷酸化。
