...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochimica et biophysica acta: BBA: International journal of biochemistry, biophysics and molecular biololgy. Proteins and Proteomics >Stability of early-stage amyloid-??(1-42) aggregation species
【24h】

Stability of early-stage amyloid-??(1-42) aggregation species

机译：早期淀粉样蛋白??（1-42）聚集物种的稳定性

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

Accumulation of aggregated amyloid-?? protein (A??) is an important feature of Alzheimer's disease. There is significant interest in understanding the initial steps of A?? aggregation due to the recent focus on soluble A?? oligomers. In vitro studies of A?? aggregation have been aided by the use of conformation-specific antibodies which recognize shape rather than sequence. One of these, OC antiserum, recognizes certain elements of fibrillar A?? across a broad range of sizes. We have observed the presence of these fibrillar elements at very early stages of A?? incubation. Using a dot blot assay, OC-reactivity was found in size exclusion chromatography (SEC)-purified A??(1-42) monomer fractions immediately after isolation (early-stage). The OC-reactivity was not initially observed in the same fractions for A??(1-40) or the aggregation-restricted A??(1-42) L34P but was detected within 1-2 weeks of incubation. Stability studies demonstrated that early-stage OC-positive A??(1-42) aggregates were resistant to 4 M urea or guanidine hydrochloride but sensitive to 1% sodium dodecyl sulfate (SDS). Interestingly, the sensitivity to SDS diminished over time upon incubation of the SEC-purified A??(1-42) solution at 4 C. Within 6-8 days the OC-positive A??42 aggregates were resistant to SDS denaturation. The progression to, and development of, SDS resistance for A??(1-42) occurred prior to thioflavin T fluorescence. In contrast, A??(1-40) aggregates formed after 6 days of incubation were sensitive to both urea and SDS. These findings reveal information on some of the earliest events in A?? aggregation and suggest that it may be possible to target early-stage aggregates before they develop significant stability. ? 2012 Elsevier B.V. All rights reserved.
机译：聚集淀粉样蛋白蛋白（Aβ）是阿尔茨海默氏病的重要特征。人们对了解A ??的初始步骤非常感兴趣。由于最近集中在可溶性A？低聚物。 A ??的体外研究通过使用识别形状而不是序列的构象特异性抗体来辅助聚集。其中之一，OC抗血清，可识别纤维状A ??的某些元素。涵盖各种尺寸。我们已经观察到在Aβ很早的阶段就存在这些纤维状元素。孵化。使用斑点印迹法，分离后（早期），在尺寸排阻色谱（SEC）纯化的Aβ（1-42）单体馏分中发现了OC反应性。最初没有在相同的馏分中观察到Aβ（1-40）或受聚合限制的Aβ（1-42）L34P的OC反应性，但在孵育的1-2周内就检测到了。稳定性研究表明，早期OC阳性的Aβ（1-42）聚集体对4 M尿素或盐酸胍具有抗性，但对1％十二烷基硫酸钠（SDS）敏感。有趣的是，经SEC纯化的Aβ（1-42）溶液于4℃保温后，对SDS的敏感性随时间而降低。在6-8天内，OC阳性的Aβ42聚集体对SDS变性具有抗性。对Aβ（1-42）的SDS抗性的进展和发展发生在硫代黄素T荧光之前。相反，孵育6天后形成的Aβ（1-40）聚集体对尿素和SDS均敏感。这些发现揭示了有关A ??最早事件的信息。聚集，并建议有可能在早期聚集形成稳定之前就将其作为目标。 ？ 2012 Elsevier B.V.保留所有权利。

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