Baum L, Hansen L, Masliah E, Saitoh T
Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla 92093-0634, USA.
Mol Chem Neuropathol. 1996 Oct-Dec;29(2-3):253-61. doi: 10.1007/BF02815006.
Highly phosphorylated tau protein is the main component of paired helical filaments (PHF), which comprise the neurofibrillary tangles (NFT) in some neurons of patients with Alzheimer disease (AD). Glycogen synthase kinase 3 (GSK3) phosphorylates tau in vitro at several sites also found to be phosphorylated in PHF-tau; tau is phosphorylated at these sites in both AD and normal control (NC) brains, although the extent of phosphorylation is far greater in tau from AD. If GSK3 levels are increased in AD, then tau phosphorylation and perhaps PHF formation may occur. To quantify GSK3, blots of AD and NC brain supernatant and particulate fractions were probed with antibodies to GSK3. In particulate fractions of AD compared to NC, GSK3 alpha immunoreactivity did not increase, but in fact, decreased 40%, and GSK3 beta immunoreactivity decreased 30%. GSK3 alpha and GSK3 beta levels correlated well with each other. GSK3 levels correlated negatively with numbers of NFT.
高度磷酸化的tau蛋白是双螺旋丝（PHF）的主要成分，双螺旋丝构成了阿尔茨海默病（AD）患者部分神经元中的神经原纤维缠结（NFT）。糖原合酶激酶3（GSK3）在体外可使tau蛋白在多个位点磷酸化，这些位点在PHF-tau中也被发现发生了磷酸化；在AD和正常对照（NC）大脑中，tau蛋白在这些位点均发生了磷酸化，尽管AD来源的tau蛋白磷酸化程度要高得多。如果AD中GSK3水平升高，那么tau蛋白磷酸化以及可能的PHF形成可能会发生。为了定量GSK3，用GSK3抗体检测AD和NC脑上清液及颗粒组分的印迹。与NC相比，在AD的颗粒组分中，GSK3α免疫反应性并未增加，实际上反而降低了40%，GSK3β免疫反应性降低了30%。GSK3α和GSK3β水平彼此相关性良好。GSK3水平与NFT数量呈负相关。
