Phospho-Tau Bar Code: Analysis of Phosphoisotypes of Tau and Its Application to Tauopathy.
Phospho-Tau Bar Code: Analysis of Phosphoisotypes of Tau and Its Application to Tauopathy.
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DOI：
10.3389/fnins.2018.00044
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发表时间：
2018
影响因子：
4.3
通讯作者：
Hisanaga SI
中科院分区：
文献类型：
--
作者：
Kimura T;Sharma G;Ishiguro K;Hisanaga SI
Tau是一种微管相关蛋白，其调节神经元轴突中微管的组装和稳定性。Tau也是神经元缠结（NFT）的主要组分，神经元缠结是阿尔茨海默病（AD）的病理标志。AD tau的特征是具有超过40个磷酸化位点的过度磷酸化。过度磷酸化的tau的聚集体也发现于统称为tau蛋白病的其他神经退行性疾病中。虽然已经对AD tau的磷酸化进行了大量研究，但尚不清楚tau蛋白病中是否存在疾病特异性磷酸化。这是由于缺乏适当的方法来分析tau蛋白磷酸化在体内。大多数以前的磷酸化研究使用一系列磷酸化位点特异性抗体进行。这些研究描述了不同磷酸化位点的相对变化，然而，很难估计磷酸化的总体、绝对和集体变化。为了克服这些问题，我们最近应用Phos-Tag技术在体外和体内分析tau蛋白磷酸化。该方法在SDS-PAGE期间根据其磷酸化状态将tau分离成许多条带，从而产生条形码外观。我们建议将tau的这种带型称为“磷酸化tau条形码”。在这篇综述文章中，我们描述了什么是新发现的tau蛋白磷酸化通过使用的Phos-Tag。我们想提出其用于tau蛋白病的尸检诊断，目前通过用抗磷酸化抗体对患病大脑进行免疫染色来完成。虽然Phos标记的SDS-PAGE与其他生化分析一样，会丢失形态学信息，但它可以提供其他类型的有价值信息，如疾病特异性磷酸化。
Tau is a microtubule-associated protein which regulates the assembly and stability of microtubules in the axons of neurons. Tau is also a major component of neurofibrillary tangles (NFTs), a pathological hallmark in Alzheimer's disease (AD). A characteristic of AD tau is hyperphosphorylation with more than 40 phosphorylation sites. Aggregates of hyperphosphorylated tau are also found in other neurodegenerative diseases which are collectively called tauopathies. Although a large number of studies have been performed on the phosphorylation of AD tau, it is not known if there is disease-specific phosphorylation among tauopathies. This is due to the lack of a proper method for analyzing tau phosphorylation in vivo. Most previous phosphorylation studies were conducted using a range of phosphorylation site-specific antibodies. These studies describe relative changes of different phosphorylation sites, however, it is hard to estimate total, absolute and collective changes in phosphorylation. To overcome these problems, we have recently applied the Phos-Tag technique to the analysis of tau phosphorylation in vitro and in vivo. This method separates tau into many bands during SDS-PAGE depending on its phosphorylation states, creating a bar code appearance. We propose calling this banding pattern of tau the “phospho-tau bar code.” In this review article, we describe what is newly discovered regarding tau phosphorylation through the use of the Phos-Tag. We would like to propose its use for the postmortem diagnosis of tauopathy which is presently done by immunostaining diseased brains with anti-phospho-antibodies. While Phos-tag SDS-PAGE, like other biochemical assays, will lose morphological information, it could provide other types of valuable information such as disease-specific phosphorylation.
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DOI：
10.1083/jcb.201007161
发表时间：
2011-02-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gauthier-Kemper A;Weissmann C;Golovyashkina N;Sebö-Lemke Z;Drewes G;Gerke V;Heinisch JJ;Brandt R
通讯作者：
Brandt R
DOI：
10.1083/jcb.101.4.1371
发表时间：
1985-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Binder LI;Frankfurter A;Rebhun LI
通讯作者：
Rebhun LI
影响因子：
4.8
作者：
DREWES, G;TRINCZEK, B;MANDELKOW, E
通讯作者：
MANDELKOW, E
影响因子：
7
作者：
Hosokawa, Tomohisa;Saito, Taro;Hisanaga, Shin-ichi
通讯作者：
Hisanaga, Shin-ichi
影响因子：
16.2
作者：
GOEDERT, M;SPILLANTINI, MG;CROWTHER, RA
通讯作者：
CROWTHER, RA