A study of abnormaly phosphorylated tau in glidl cells
A study of abnormaly phosphorylated tau in glidl cells
批准号:
08680830
负责人:
IKEDA Kenji
金额:
$1.15万
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
项目状态:
已结题
起止时间:
1996 至 1997
中文摘要
出现在胶质细胞中的tau阳性包涵体被称为胶质纤维缠结,或者更简单地说,神经胶质缠结。这些星形细胞包括簇状星形细胞、棘状星形细胞、卷曲小体和嗜银线。后两种结构见于少突胶质细胞。神经胶质缠结中的tau蛋白被过度磷酸化,其免疫组织化学特征与神经纤维缠结相似,不同之处在于它不存在外显子2和外显子3选择性剪接的表位。与神经原纤维缠结相比,神经胶质缠结中很少出现固体细丝。NFTs相关分子如泛素、载脂蛋白E、α1抗胰凝乳素和硫酸乙酰肝素都不存在于神经胶质缠结中。这些特征表明,神经胶质缠结类似于出现在神经元中的椒盐,被认为代表了NFTs的早期阶段。神经退行性疾病中的tau病理表现为异质性。免疫组织化学显示原代培养的大鼠星形胶质细胞中存在部分磷酸化的tau,包括磷酸化和非磷酸化的tau抗体以及免疫印迹。在进一步培养、的过程中,tau的免疫原性逐渐减弱,然而,连续和反复暴露于钙离子载体可维持培养的星形胶质细胞tau的免疫反应性,并且在Ser396处发生了磷酸化。电子显微镜显示,除细胞核和线粒体外,tau弥漫分布于星形胶质细胞内,但未见丝状集合体。
英文摘要
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.
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Ikeda K,et al: "Alzheimer's disease:Biology,Diagnosis and Therapeutics" John Wiley & Sons, 9 (1997)
Ikeda K 等人:“阿尔茨海默病:生物学、诊断和治疗”John Wiley
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Ikeda K: "Principles of neural aging" Elsevier Science, 15 (1997)
池田 K:“神经衰老的原理”Elsevier Science,15 (1997)
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池田 研二: "神経変性疾患におけるグリアの細胞骨格異常、総論と分類" 脳神経. 48. 885-894 (1996)
Kenji Ikeda:“神经退行性疾病中的胶质细胞骨架异常,一般回顾和分类”《颅神经病学》48. 885-894 (1996)。
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Ikeda K: "Principles of neural aging." Elsevier Science B.V., 461 (1997)
Ikeda K:“神经衰老的原理。”
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Ikeda K: "Basic pathology of corticobasal degeneration." Neuropathology. 17. 127-133 (1997)
Ikeda K:“皮质基底节变性的基本病理学。”
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