...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>ACS Omega >Investigating in Vitro Amyloid Peptide 1–42 Aggregation: Impact of Higher Molecular Weight Stable Adducts
【24h】

Investigating in Vitro Amyloid Peptide 1–42 Aggregation: Impact of Higher Molecular Weight Stable Adducts

机译：研究体外淀粉样肽1-42聚集：高分子量稳定加合物的影响

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The self-assembly of amyloid peptides (Aβ), in particular Aβ1–42, into oligomers and fibrils is one of the main pathological events related to Alzheimer’s disease. Recent studies have demonstrated the ability of carbon monoxide-releasing molecules (CORMs) to protect neurons and astrocytes from Aβ1–42 toxicity. In fact, CORMs are able to carry and release controlled levels of CO and are known to exert a wide range of anti-inflammatory and anti-apoptotic activities at physiologically relevant concentrations. In order to investigate the direct effects of CORMs on Aβ1–42, we studied the reactivity of CORM-2 and CORM-3 with Aβ1–42in vitro and the potential inhibition of its aggregation by mass spectrometry (MS), as well as fluorescence and circular dichroism spectroscopies. The application of an electrospray ionization-MS (ESI-MS) method allowed the detection of stable Aβ1–42/CORMs adducts, involving the addition of the Ru(CO)2 portion of CORMs at histidine residues on the Aβ1–42 skeleton. Moreover, CORMs showed anti-aggregating properties through formation of stable adducts with Aβ1–42 as demonstrated by a thioflavin T fluorescence assay and MS analysis. As further proof, comparison of the CD spectra of Aβ1–42 recorded in the absence and in the presence of CORM-3 at a 1:1 molar ratio showed the ability of CORM-3 to stabilize the peptide in its soluble, unordered conformation, thereby preventing its misfolding and aggregation. This multi-methodological investigation revealed novel interactions between Aβ1–42 and CORMs, contributing new insights into the proposed neuroprotective mechanisms mediated by CORMs and disclosing a new strategy to divert amyloid aggregation and toxicity.
机译：淀粉样肽（Aβ），特别是Aβ1-42的自组装成寡聚物和原纤维是与阿尔茨海默氏病有关的主要病理事件之一。最近的研究表明，一氧化碳释放分子（CORM）能够保护神经元和星形胶质细胞免受Aβ1-42毒性。实际上，CORM能够携带和释放受控水平的CO，并且已知在生理相关浓度下具有广泛的抗炎和抗凋亡活性。为了研究CORM对Aβ1-42的直接作用，我们研究了CORM-2和CORM-3与Aβ1-42的体外反应性，以及质谱（MS）以及荧光和质谱法对它的聚集的潜在抑制作用。圆二色性光谱学。电喷雾电离质谱（ESI-MS）方法的应用允许检测稳定的Aβ1-42/ CORMs加合物，包括在Aβ1-42骨架上的组氨酸残基上添加CORM的Ru（CO）2部分。此外，CORRMs通过与Aβ1-42形成稳定的加合物而显示出抗聚集特性，这是通过硫代黄素T荧光分析和MS分析证明的。作为进一步的证明，在不存在CORM-3和存在CORM-3且摩尔比为1：1的情况下记录的Aβ1-42的CD光谱的比较表明，CORM-3具有将肽稳定在其可溶性无序构象的能力，从而防止其错误折叠和聚集。这项多方法研究揭示了Aβ1-42与CORM之间的新型相互作用，为由CORM介导的拟议神经保护机制提供了新见识，并揭示了转移淀粉样蛋白聚集和毒性的新策略。

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