Iimoto D S, Masliah E, DeTeresa R, Terry R D, Saitoh T
University of California, San Diego, School of Medicine, La Jolla, CA 92093.
Brain Res. 1990 Jan 22;507(2):273-80. doi: 10.1016/0006-8993(90)90282-g.
Abnormal protein phosphorylation has been identified in Alzheimer's disease (AD) for several proteins including a Mr 60,000 protein, a Mr 86,000 protein and a microtubule-associated protein tau. The Mr 86,000 protein is phosphorylated by protein kinase C, whereas protein kinases responsible for other aberrant phosphorylation reactions are not known. In addition to protein kinase C, another kinase, casein kinase II (CK-II), has now been shown to be aberrant in AD. The spermine-dependent CK-II activity is reduced by 84% in AD and the amount of CK-II as determined by its immunoreactivity on a Western blot is reduced by 63%. Furthermore, the distribution of CK-II in AD is altered. Although the neuronal cell body reacts well with CK-II antisera in the normal cortex, the non-tangle-bearing neurons in the AD cortex showed a 15-30% decrease in anti-CK-II immunoreactivity. The neurofibrillary tangles, on the other hand, stain very strongly with rabbit anti-CK-II and indicates that CK-II may be involved in the pathology of AD. The study of CK-II immunoreactivity for dementing diseases other than AD revealed a similar reduction, suggesting the CK-II involvement in the common process of neurodegeneration.
在阿尔茨海默病（AD）中已发现几种蛋白质存在异常的蛋白质磷酸化，包括一种分子量为60,000的蛋白质、一种分子量为86,000的蛋白质和一种微管相关蛋白tau。分子量为86,000的蛋白质被蛋白激酶C磷酸化，而负责其他异常磷酸化反应的蛋白激酶尚不清楚。除蛋白激酶C外，另一种激酶——酪蛋白激酶II（CK-II），现已证明在AD中也存在异常。在AD中，精胺依赖性CK-II活性降低了84%，通过蛋白质免疫印迹法测定的CK-II量减少了63%。此外，AD中CK-II的分布也发生了改变。虽然在正常皮质中神经元细胞体与CK-II抗血清反应良好，但AD皮质中无神经缠结的神经元抗CK-II免疫反应性降低了15%-30%。另一方面，神经原纤维缠结用兔抗CK-II染色非常强烈，表明CK-II可能参与了AD的病理过程。对除AD以外的痴呆疾病的CK-II免疫反应性研究显示出类似的降低，提示CK-II参与了神经退行性变的共同过程。
