Pathological-Like Assembly of TAU Induced by a Paired Helical Filament Core Expressed at the Plasma Membrane
Pathological-Like Assembly of TAU Induced by a Paired Helical Filament Core Expressed at the Plasma Membrane
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DOI：
10.3233/jad-2009-1198
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发表时间：
2009-01-01
影响因子：
4
通讯作者：
Antonio Meraz-Rios, Marco
中科院分区：
文献类型：
--
作者：
Campos-Pena, Victoria;Tapia-Ramirez, Jose;Antonio Meraz-Rios, Marco
阿尔茨海默病的标志是tau蛋白病理聚集成成对的螺旋细丝和神经原纤维缠结。本文研究了嵌合tau分子在COS-7细胞质膜上的异常表达和定位及其与tau聚合的关系。这些蛋白的过度表达，与tau441或tau391结合，诱导tau蛋白组装成β -褶层，这些褶层可被Thiazin红识别。免疫电镜分析显示，靠近质膜的细丝与阿尔茨海默病中发现的细丝相似。在H2O2或冈田酸处理下，质膜相关嵌合tau蛋白捕获全长tau的能力增加。这表明，过度磷酸化或氧化环境都可能影响细胞的生化特性，从而导致成对螺旋细丝的组装。质膜上tau蛋白定位的改变可能在病理性tau的组装中起关键作用。
The hallmark of Alzheimer's disease is the pathological aggregation of tau proteins into paired helical filaments and neurofibrillary tangles. This paper evaluates the abnormal expression and localization of chimeric tau molecules at the plasma membrane of COS-7 cells and its relationship with tau polymerization. Overexpression of these proteins, in combination with either tau441 or tau391, induces tau to assemble into beta-pleated sheets that are recognized by Thiazin red. Immunoelectromicroscopy analysis revealed the presence of filaments close to the plasma membrane resembling those found in Alzheimer's disease. The capacity of plasma membrane-associated chimeric tau proteins to capture full length tau was increased in the presence of H2O2 or okadaic acid treatments. This suggests that hyperphosphorylation or an oxidative environment could both influence the biochemical properties of the cell that lead to assembly of paired helical filaments. The altered localization of tau protein at the plasma membrane could play a key role in the assembly of pathological tau.