Preferential labeling of Alzheimer neurofibrillary tangles with antisera for tau protein kinase (TPK)I glycogen synthase kinase-3 beta and cyclin-dependent kinase 5, a component of TPK II
Preferential labeling of Alzheimer neurofibrillary tangles with antisera for tau protein kinase (TPK)I glycogen synthase kinase-3 beta and cyclin-dependent kinase 5, a component of TPK II
复制标题
DOI：
10.1007/s004010050513
复制
发表时间：
1996-09-01
影响因子：
12.7
通讯作者：
Imahori, K
中科院分区：
文献类型：
--
作者：
Yamaguchi, H;Ishiguro, K;Imahori, K
使用免疫组织化学，我们检查了四种类型的脯氨酸定向激酶在对照大鼠大脑以及非痴呆老年人受试者、阿尔茨海默病受试者和唐氏综合症受试者大脑中的定位。这四种激酶是：细胞周期蛋白依赖性激酶（cdk）5，tau蛋白激酶（TPK）II的组分; TPK I/糖原合成酶激酶（GSK）-3 β; GSK-3 α;和促分裂原活化蛋白激酶（MAPK/ERK 2）。据报道，这些激酶中的每一种都能在体外促进tau蛋白的过度磷酸化。激酶基本上位于神经元中，尽管标记的强度和分布各不相同。cdk 5的抗血清显示出最优先和一致的标记神经元内神经元缠结（NFT）。TPK I/GSK-3 β的抗血清也标记神经元内NFT。TPK I/GSK-3 β和tau 1的双重免疫标记显示TPK T/GSK-3 β与NFT密切相关。GSK-3 α的抗血清标记神经元较弱，标记强度在有无NFT的神经元之间没有差异。MAPK抗血清仅标记皮层浅层神经元，而NFT在皮层浅层和深层均有标记。这些发现表明，cdk 5和TPK I/GSK-3 β是体内产生过度磷酸化tau蛋白的关键重要激酶，过度磷酸化tau蛋白是NFT中成对螺旋丝的主要成分。
Using immunohistochemistry, we examined the localization of four types of proline-directed kinases in the brains of control rats and in the brains of non-demented aged human subjects, subjects with Alzheimer's disease and those with Down's syndrome. The four kinases were: cyclin-dependent kinase (cdk) 5, a component of tau protein kinase (TPK) II; TPK I/glycogen synthase kinase (GSK)-3 beta; GSK-3 alpha; and mitogen-activated protein kinase (MAPK/ERK2). Each of these kinases has been reported to promote the hyperphosphorylation of tau protein in vitro. The kinases were located essentially in neurons, although the intensity and distribution of labeling varied. Antiserum for cdk5 showed the most preferential and consistent labeling of intraneuronal neurofibrillary tangles (NFT). Antiserum for TPK I/GSK-3 beta also labeled intraneuronal NFT. Double immunolabeling for TPK I/GSK-3 beta and tau1 showed that TPK T/GSK-3 beta was closely associated with NFT. Antiserum for GSK-3 alpha labeled neurons weakly, and the intensity of labeling did not differ between neurons with and without NFT. Antiserum for MAPK labeled neurons in superficial cortical layers, but NFT appeared in both superficial and deep cortical layers. These findings suggest that cdk5 and TPK I/GSK-3 beta are the critically important kinases for the generation in vivo of hyperphosphorylated tau, the main component of the paired helical filaments in NFT.