Iqbal K, Grundke-Iqbal I
Chemical Neuropathology Laboratory, New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314, USA.
Ann N Y Acad Sci. 1996 Jan 17;777:132-8. doi: 10.1111/j.1749-6632.1996.tb34411.x.
Microtubule-associated protein tau is abnormally hyperphosphorylated in the brain of patients with Alzheimer's disease (AD) and the abnormal tau is the major protein subunit of paired helical filaments (PHF). The abnormal phosphorylation of tau probably precedes its polymerization into PHF. The abnormal tau does not bind to tubulin, but competes with tubulin in binding to normal tau and thereby inhibits the assembly of microtubules in the affected neurons. The abnormal tau can be dephosphorylated enzymatically and by this way its microtubule assembly promoting activity can be restored. The activities of protein phosphatases might be decreased in the affected neurons in AD brain, allowing the abnormal hyperphosphorylation of tau. Neurofibrillary degeneration can probably be inhibited by increasing the activities of protein phosphatases in the brain of patients with Alzheimer's disease.
在阿尔茨海默病（AD）患者的大脑中，微管相关蛋白tau异常过度磷酸化，且异常的tau是双螺旋丝（PHF）的主要蛋白质亚基。tau的异常磷酸化可能先于其聚合成PHF。异常的tau不与微管蛋白结合，但在与正常tau结合时与微管蛋白竞争，从而抑制受影响神经元中微管的组装。异常的tau可通过酶促去磷酸化，从而恢复其促进微管组装的活性。在AD大脑中，受影响的神经元中蛋白磷酸酶的活性可能会降低，从而使tau发生异常的过度磷酸化。通过增加阿尔茨海默病患者大脑中蛋白磷酸酶的活性，可能会抑制神经原纤维变性。
