Tau clearance mechanisms and their possible role in the pathogenesis of Alzheimer disease.
Tau clearance mechanisms and their possible role in the pathogenesis of Alzheimer disease.
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DOI：
10.3389/fneur.2013.00122
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发表时间：
2013-09-03
影响因子：
3.4
通讯作者：
Johnson GV
中科院分区：
文献类型：
--
作者：
Chesser AS;Pritchard SM;Johnson GV
阿尔茨海默病（AD）的定义性病理特征之一是tau蛋白的神经元内积累。形成这些积累的tau在翻译后和构象上都发生了改变，现在有重要证据表明这些修饰的tau种类的可溶形式是有毒实体，而不是不可溶的神经原纤维缠结。然而，关于tau的哪些特定病理形式是AD中神经元功能障碍和死亡的贡献者，仍然存在值得注意的争论。鉴于异常形式的tau的增加在AD的神经变性过程中起作用，人们越来越感兴趣地了解从细胞中去除tau的降解途径，以及这些不同途径对各种形式的tau的选择性。事实上，人们可以推测，选择性去除某些病理形式的tau的途径中的缺陷可能在AD中起关键作用。在这篇综述中，我们将讨论不同的蛋白水解和降解机制，可能参与从细胞中去除tau蛋白。还将考虑这些不同降解途径的缺陷如何导致AD中tau的异常积累。此外，将解决特定tau种类选择性靶向给定降解途径以从细胞中清除的问题。
One of the defining pathological features of Alzheimer disease (AD) is the intraneuronal accumulation of tau. The tau that forms these accumulations is altered both posttranslationally and conformationally, and there is now significant evidence that soluble forms of these modified tau species are the toxic entities rather than the insoluble neurofibrillary tangles. However there is still noteworthy debate concerning which specific pathological forms of tau are the contributors to neuronal dysfunction and death in AD. Given that increases in aberrant forms of tau play a role in the neurodegeneration process in AD, there is growing interest in understanding the degradative pathways that remove tau from the cell, and the selectivity of these different pathways for various forms of tau. Indeed, one can speculate that deficits in a pathway that selectively removes certain pathological forms of tau could play a pivotal role in AD. In this review we will discuss the different proteolytic and degradative machineries that may be involved in removing tau from the cell. How deficits in these different degradative pathways may contribute to abnormal accumulation of tau in AD will also be considered. In addition, the issue of the selective targeting of specific tau species to a given degradative pathway for clearance from the cell will be addressed.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
10.1097/01.jnen.0000196133.74087.cb
发表时间：
2006-01-01
影响因子：
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作者：
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通讯作者：
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