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有读书笔记有附件Transmission and spreading of tauopathy in transgenic mouse brain

热1 管理员 添加于 2009-8-4 18:03 | 2653 次阅读 | 1 个评论

  •  作 者

    Clavaguera F, Bolmont T, Crowther RA, Abramowski D, Frank S, Probst A, Fraser G, Stalder AK, Beibel M, Staufenbiel M, Jucker M, Goedert M, Tolnay M

  •  摘 要

    Hyperphosphorylated tau makes up the filamentous intracellular inclusions of several neurodegenerative diseases, including Alzheimer's disease. In the disease process, neuronal tau inclusions first appear in the transentorhinal cortex from where they seem to spread to the hippocampal formation and neocortex. Cognitive impairment becomes manifest when inclusions reach the hippocampus, with abundant neocortical tau inclusions and extracellular beta-amyloid deposits being the defining pathological hallmarks of Alzheimer's disease. An abundance of tau inclusions, in the absence of beta-amyloid deposits, defines Pick's disease, progressive supranuclear palsy, corticobasal degeneration and other diseases. Tau mutations cause familial forms of frontotemporal dementia, establishing that tau protein dysfunction is sufficient to cause neurodegeneration and dementia. Thus, transgenic mice expressing mutant (for example, P301S) human tau in nerve cells show the essential features of tauopathies, including neurodegeneration and abundant filaments made of hyperphosphorylated tau protein. By contrast, mouse lines expressing single isoforms of wild-type human tau do not produce tau filaments or show neurodegeneration. Here we have used tau-expressing lines to investigate whether experimental tauopathy can be transmitted. We show that injection of brain extract from mutant P301S tau-expressing mice into the brain of transgenic wild-type tau-expressing animals induces assembly of wild-type human tau into filaments and spreading of pathology from the site of injection to neighbouring brain regions.

  •  详细资料

    • 关键词: Animals; Blotting, Western; Brain/*metabolism/*pathology; Humans; Immunohistochemistry; Mice; Mice, Transgenic; Tauopathies/*genetics/*pathology; tau Proteins/genetics/metabolism/physiology
    • 文献种类:期刊
    • 期刊名称: Nature Cell Biology
    • 期刊缩写: Nat Cell Biol
    • 期卷页: 2009年  第11卷 第7期 909-913页
    • 地址: Department of Neuropathology, Institute of Pathology, University of Basel, Switzerland
    • ISBN: 1476-4679
    • 备注:PMID:19503072

  •  标 签

    生物研究进展 

  • 相关链接 DOI URL 

  •  附 件

    PDF附件全文 

  •  管理员 的文献笔记  订阅

    研究人员从阿尔茨海默氏症患者大脑中提取出纤维状纠缠物，当他们将这些纠缠物注入健康小鼠的大脑后，小鼠的大脑中也形成了类似的纠缠物，新成果发表 在日前在线出版的《自然—细胞生物学》期刊上。新发现表明，这种纠缠物有传染性，而且可能与朊病毒类似，朊病毒与传染性脑疾病如疯牛病和人类库兹德-贾克 氏病等相关。

    微管相关蛋白是阿尔茨海默氏症患者大脑神经元纤维缠结的组成部分。Markus Tolnay和同事从表达一种变异人类tau蛋白质的小鼠大脑中提取出部分脑组织，并将这些大脑提取物注入普通小鼠的大脑特定区域。他们发现，这些大脑提 取物引导人类tau蛋白质在普通小鼠大脑内聚集，形成神经元纤维缠结。此外，这些新形成的缠结扩散到了大脑中的附近区域。

    以前，研究人员在tau蛋白疾病家族中神经退化性疾病患者的体内观察到了tau包含物的形成，但认为它们没有传染性。而朊蛋白质则被认为具有传染性，它们因折叠成非正常结构而聚集在一起，这样，它们就能将正常的配对物转化为类似的非正常结构。

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facelist doodle 涂鸦板

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