...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Effects of Tau Domain-Specific Antibodies and Intravenous lmmunoglobulin on Tau Aggregation and Aggregate Degradation
【24h】

Effects of Tau Domain-Specific Antibodies and Intravenous lmmunoglobulin on Tau Aggregation and Aggregate Degradation

机译：Tau结构域特异性抗体和静脉免疫球蛋白对Tau聚集和聚集降解的影响

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Tau pathology, including neurofibrillary tangles, develops in Alzheimer's disease (AD). The aggregation and hyperphosphorylation of tau are potential therapeutic targets for AD. Administration of anti-tau antibodies reduces tau pathology in transgenic "tauopathy" mice; however, the optimal tau epitopes and conformations to target are unclear. Also unknown is whether intravenous immunoglobulin (IVIG) products, currently being evaluated in AD trials, exert effects on pathological tau. This study examined the effects of anti-tau antibodies targeting different tau epitopes and the IVIG Gammagard on tau aggregation and preformed tau aggregates. Tau aggregation was assessed by transmission electron microscopy and fluorescence spectroscopy, and the binding affinity of the anti-tau antibodies for tau was evaluated by enzyme-linked immunosorbent assays. Antibodies used were anti-tau 1-150 ("D-8"), anti-tau 259-266 ("Paired-262"), anti-tau 341-360 ("A-10"), and anti-tau 404-441 ("Tau-46"), which bind to tau's N-terminus, microtubule binding domain (MBD) repeat sequences R1 and R4, and the C-terminus, respectively. The antibodies Paired-262 and A-10, but not D-8 and Tau-46, reduced tau fibrillization and degraded preformed tau aggregates, whereas the IVIG reduced tau aggregation but did not alter preformed aggregates. The binding affinities of the antibodies for the epitope for which they were specific did not appear to be related to their effects on tau aggregation. These results confirm that antibody binding to tau's MBD repeat sequences may inhibit tau aggregation and indicate that such antibodies may also degrade preformed tau aggregates. In the presence of anti-tau antibodies, the resulting tau morphologies were antigen-dependent. The results also suggested the possibility of different pathways regulating antibody-mediated inhibition of tau aggregation and antibody-mediated degradation of preformed tau aggregates.
机译：Tau病理，包括神经原纤维缠结，在阿尔茨海默氏病（AD）中发展。 τ的聚集和过度磷酸化是AD的潜在治疗靶标。抗tau抗体的施用可降低转基因“ tauopathy”小鼠的tau病理;然而，尚不清楚最佳的tau表位和目标构象。同样未知的是，目前正在AD试验中评估的静脉免疫球蛋白（IVIG）产品是否对病理性tau产生影响。这项研究检查了针对不同tau表位的抗tau抗体和IVIG Gammagard对tau聚集体和预先形成的tau聚集体的影响。通过透射电子显微镜和荧光光谱评估Tau聚集，并且通过酶联免疫吸附测定法评估抗tau抗体对tau的结合亲和力。使用的抗体是抗tau 1-150（“ D-8”），抗tau 259-266（“ Paired-262”），抗tau 341-360（“ A-10”）和抗tau 404 -441（“ Tau-46”），其结合至tau的N端，微管结合域（MBD）分别重复序列R1和R4，以及C端。 Paired-262和A-10抗体，但D-8和Tau-46抗体没有，减少了tau原纤维化并降解了预形成的tau聚集体，而IVIG降低了tau聚集，但没有改变预形成的聚集体。抗体对它们特异的表位的结合亲和力似乎与它们对tau聚集的作用无关。这些结果证实了结合至tau的MBD重复序列的抗体可以抑制tau聚集，并且表明这种抗体也可以降解预先形成的tau聚集体。在存在抗tau抗体的情况下，产生的tau形态是抗原依赖性的。结果还表明，可能存在不同途径调节抗体介导的tau聚集抑制和抗体介导的预制tau聚集体降解的途径。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号