TOC1: characterization of a selective oligomeric tau antibody.
TOC1: characterization of a selective oligomeric tau antibody.
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DOI：
10.3233/jad-131235
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Binder LI
中科院分区：
文献类型：
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作者：
Ward SM;Himmelstein DS;Lancia JK;Fu Y;Patterson KR;Binder LI
本文提出的工作解决了tau病理的一个特定部分，纤维前低聚物，现在被认为是阿尔茨海默病和其他神经退行性tau病的重要病理成分。在之前的工作中，我们生成了一种针对纯化的重组交联tau二聚体的抗体，称为tau寡聚物1 （TOC1）。TOC1识别tau寡聚物，其免疫反应性在阿尔茨海默病大脑中升高。在本报告中，我们扩展了先前的研究，表明TOC1选择性地标记单体或聚合物上的tau低聚物，并且TOC1在其他神经退行性tau病中也具有反应性。利用一系列跨越tau分子的缺失突变体，我们进一步证明TOC1在氨基酸209-224中有一个连续的表位，位于所谓的脯氨酸富区。结合之前的研究，我们的数据表明TOC1是一种构象依赖性抗体，其表位在二聚化和寡聚化时显示，但在聚合物形成时再次隐藏。TOC1抗体的这一特性进一步支持了其作为一种强大的生化工具的潜力，可用于更好地研究tau在神经退行性疾病中的作用。
The work presented herein addresses a specific portion of the tau pathology, pre-fibrillar oligomers, now thought to be important pathological components in Alzheimer’s disease and other neurodegenerative tauopathies. In previous work, we generated an antibody against purified recombinant cross-linked tau dimers, called Tau Oligomeric Complex 1 (TOC1). TOC1 recognizes tau oligomers and its immunoreactivity is elevated in Alzheimer’s disease brains. In this report, we expand upon the previous study to show that TOC1 selectively labels tau oligomers over monomers or polymers, and that TOC1 is also reactive in other neurodegenerative tauopathies. Using a series of deletion mutants spanning the tau molecule, we further demonstrate that TOC1 has one continuous epitope located within amino acids 209–224, in the so-called proline rich region. Together with the previous study, our data indicates that TOC1 is a conformation-dependent antibody whose epitope is revealed upon dimerization and oligomerization, but concealed again as polymers form. This characterization of the TOC1 antibody further supports its potential as a powerful biochemical tool that can be used to better investigate the involvement of tau in neurodegenerative diseases.