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进行性核上性麻痹中的神经原纤维缠结含有与阿尔茨海默病PHFtau中鉴定出的相同的tau表位。

Neurofibrillary tangles in progressive supranuclear palsy contain the same tau epitopes identified in Alzheimer's disease PHFtau.

作者信息

Schmidt M L, Huang R, Martin J A, Henley J, Mawal-Dewan M, Hurtig H I, Lee V M, Trojanowski J Q

机构信息

Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-4283, USA.

出版信息

J Neuropathol Exp Neurol. 1996 May;55(5):534-9. doi: 10.1097/00005072-199605000-00006.

Abstract

Neurofibrillary tangle (NFT)-rich brain samples from patients with progressive supranuclear palsy (PSP) or Alzheimer's disease (AD) were probed with a large panel of anti-tau antibodies to compare the species of tau present in PSP and AD NFTs by immunohistochemistry and Western blot methods. These antibodies have been shown to recognize phosphate-independent or -dependent epitopes that extend from the amino to the carboxy terminal domains of normal brain tau and the abnormal tau in the paired helical filaments (PHFs) of AD NFTs (PHFtau). The immunohistochemical studies showed that all of the tau epitopes detected in brainstem PSP NFTs also were found in hippocampal AD NFTs and vice versa. While Western blots demonstrated 2 PHFtau-like immunobands in PSP brainstem, a triplet of PHFtau proteins were seen in the AD and PSP hippocampus. Despite differences in the distribution, ultrastructure and immunoblot profile of NFTs in PSP and AD, the same constellation of tau epitopes is present in the abnormal tau proteins in PSP and AD NFTs. Thus, the generation of abnormal tau proteins in PSP (PSPtau) and AD (PHFtau) may have similar adverse biological consequences in both diseases.

摘要

使用大量抗tau抗体对进行性核上性麻痹(PSP)或阿尔茨海默病(AD)患者富含神经原纤维缠结(NFT)的脑样本进行检测,通过免疫组织化学和蛋白质印迹法比较PSP和AD NFT中存在的tau种类。这些抗体已被证明可识别从正常脑tau的氨基端到羧基端结构域以及AD NFT的成对螺旋丝(PHF)中的异常tau延伸出的不依赖或依赖磷酸化的表位(PHFtau)。免疫组织化学研究表明,在脑干PSP NFT中检测到的所有tau表位在海马AD NFT中也能找到,反之亦然。虽然蛋白质印迹显示PSP脑干中有两条类似PHFtau的免疫条带,但在AD和PSP海马中可见PHFtau蛋白的三联体。尽管PSP和AD中NFT的分布、超微结构和免疫印迹图谱存在差异,但PSP和AD NFT的异常tau蛋白中存在相同的tau表位组合。因此,PSP(PSPtau)和AD(PHFtau)中异常tau蛋白的产生在这两种疾病中可能具有相似的不良生物学后果。

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