Grundke-Iqbal I, Iqbal K
New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
Prog Clin Biol Res. 1989;317:745-53.
In Alzheimer disease the neuronal cytoskeleton is severely affected with the accumulation of paired helical filaments (PHF) in selected neurons, and a defect of microtubule assembly. Although the biochemistry of PHF is not yet completely established, the microtubule associated protein tau has been identified as one of their components. Tau in PHF is abnormally phosphorylated. This alteration of tau is present at very early stages of tangles formation. These findings indicate a defect of the neuronal phosphorylation/dephosphorylation system in Alzheimer brain. It is hypothesized that abnormal phosphorylation, together with other modifications might stabilize tau and facilitate its polymerization together with some other as yet to be identified components to PHF. The microtubule assembly defect might have direct functional consequences via compromised axoplasmic flow and neurotransmission.
在阿尔茨海默病中，神经元细胞骨架受到严重影响，特定神经元中出现双螺旋丝（PHF）积聚以及微管组装缺陷。尽管PHF的生物化学性质尚未完全明确，但已确定微管相关蛋白tau是其组成成分之一。PHF中的tau发生了异常磷酸化。这种tau的改变在缠结形成的非常早期阶段就已存在。这些发现表明阿尔茨海默病大脑中神经元磷酸化/去磷酸化系统存在缺陷。据推测，异常磷酸化以及其他修饰可能会使tau稳定，并促进其与其他一些尚未确定的成分一起聚合成PHF。微管组装缺陷可能通过受损的轴浆运输和神经传递产生直接的功能后果。
