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A study of abnormaly phosphorylated tau in glidl cells

glidl细胞异常磷酸化tau蛋白的研究

基本信息

批准号：
08680830
负责人：
IKEDA Kenji
金额：
$ 1.15万
依托单位：
Tokyo Institute of Psychiatry
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

Tau-positive inclusions that occur in glial cells are called glial fibrillary tangles or, more simply, glial tangles. These include tuft-shaped astrocytes, thorn-shaped astrocytes, coiled bodies and argyrophilic threads. The latter two sltructures occur in oligodendroglia. The tau protein in glial tangles is hyperphosphorylated and has similar immunohistochemical profiles to that in neurofibrillary tangles (NFTs) except that there are no epitopes derived from alternatively spliced exon 2 and 3. In contrast to NFTs, glial tangles rarely show solid filaments. Such NFTs-associated molecules as ubiquitin, apolipoprotein E,alpha1-antichymotrypsin and heparan sulfate are all absent from glial tangles. These characteristics suggest that glial tangles resemble the pretangles which occur in neurons adn are thought to represent an early stage of NFTs. Tau pathology in neurodegenerative diseases takes heterogenous forms.Manifestation of partially phosphorylated tau in rat primary culture astrocytes was shown immunohistochemically by phosphorylated as well as non-phosphorylated tau antibodies and by immunoblots. Immunogenicity for tau gradually diminished during further culture、however, continuous and recurrent exposure to calcium ionophore maintained immunoreactivity for tau in culture astrocytes and moreover occurred phosphorylation at Ser 396. Electron microscopy showed tau distributed diffusely in the experimental astrocytes except for in the nucleus and mitochondria but no filamentous assembly was observed.

神经胶质细胞中出现的 Tau 阳性包涵体称为神经胶质原纤维缠结，或更简单地说，神经胶质缠结。这些包括簇状星形胶质细胞、刺状星形胶质细胞、卷曲体和嗜银线。后两种结构出现在少突胶质细胞中。神经胶质缠结中的 tau 蛋白过度磷酸化，并且具有与神经原纤维缠结 (NFT) 相似的免疫组织化学特征，只是不存在来自可变剪接的外显子 2 和 3 的表位。与 NFT 相比，神经胶质缠结很少显示实心丝。神经胶质缠结中不存在泛素、载脂蛋白 E、α1-抗胰凝乳蛋白酶和硫酸乙酰肝素等 NFT 相关分子。这些特征表明，神经胶质缠结类似于神经元中发生的前缠结，并且被认为代表了 NFT 的早期阶段。神经退行性疾病中的 Tau 病理学具有异质性形式。通过磷酸化和非磷酸化 tau 抗体以及免疫印迹，免疫组织化学显示了大鼠原代培养物星形胶质细胞中部分磷酸化 tau 的表现。在进一步培养过程中，tau的免疫原性逐渐减弱，然而，持续和反复暴露于钙离子载体，培养的星形胶质细胞中tau保持了免疫反应性，并且在Ser 396处发生磷酸化。电镜观察显示，除了细胞核和线粒体外，tau在实验星形胶质细胞中广泛分布，但没有观察到丝状组装。