Glycogen synthase kinase 3 alteration in Alzheimer disease is related to neurofibrillary tangle formation
Glycogen synthase kinase 3 alteration in Alzheimer disease is related to neurofibrillary tangle formation
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DOI：
10.1007/bf02815006
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发表时间：
1996-10-01
期刊：
影响因子：
--
通讯作者：
Saitoh, T
中科院分区：
文献类型：
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作者：
Baum, L;Hansen, L;Saitoh, T
高度磷酸化的tau蛋白是阿尔茨海默病（AD）患者神经元中神经元缠结（NET）的主要组成部分。糖原合酶激酶3（GSK 3）在体外在几个位点磷酸化tau，也发现在PHF-tau中磷酸化;在AD和正常对照（NC）脑中，tau在这些位点磷酸化，尽管在AD的tau中磷酸化的程度要大得多。如果GSK3水平在AD中增加，则可能发生tau磷酸化和PHF形成。为了定量GSK 3，用抗GSK 3的抗体探测AD和NC脑上清液和颗粒级分的印迹。与NC相比，在AD的颗粒组分中，GSK 3 β免疫反应性没有增加，但实际上降低了40%，GSK 3 β免疫反应性降低了30%。GSK3 α和GSK3 β水平彼此相关性良好。GSK3水平与NFT数量呈负相关。
Highly phosphorylated tau protein is the main component of paired helical filaments (PHF), which comprise the neurofibrillary tangles (NET) 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 beta 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.