XAS INVESTIGATION OF ALZHEIMER'S BETA-AMYLOID FIBRILS

阿尔茨海默病 β-淀粉样原纤维的 XAS 研究

• 批准号: 7954215
• 负责人: ROBERT A SCOTT
• 金额: $ 0.31万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954215
• 关键词: Amyloid beta-Protein; Binding; Computer Retrieval of Information on Scientific Projects Database; Freezing; Funding; Grant; Heavy Metals; In Vitro; Institution; Investigation; Metals; Morphology; Process; Research; Research Personnel; Resources; Site; Source; Spectrum Analysis; Structure; Techniques; Time; United States National Institutes of Health; absorption; amyloid fibril formation; interest; neurotoxicity; physical separation; structural biology; synchrotron radiation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose to use x-ray absorption spectroscopy to characterize heavy metal sites (Zn(II) and Cu(II)) involved in the formation of amyloid fibrils. Zn(II) and Cu(II) have emerged as important factors in aggregation of amyloid beta (Abeta) peptide and the neurotoxicity of this process. We propose to investigate the local structure of Zn(II) and Cu(II) binding to fibrils formed with a number of truncated Abeta peptides in vitro. Of particular interest is the relationship between local metal coordination and aggregate morphology. It has also been shown that assembly of Abeta peptide is a nucleation-dependent process, which would allow us to follow the process over time, by flash-freeze techniques and/or physical separation, from aggregate nucleation through propagation of fibril formation.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 我们建议使用X射线吸收光谱来表征与淀粉样蛋白原纤维形成有关的重金属位点（Zn（ii）和Cu（ii））。 Zn（II）和Cu（II）已成为淀粉样β（ABETA）肽聚集的重要因素以及该过程的神经毒性。我们建议研究Zn（II）和Cu（II）与在体外与许多截短的Abeta肽形成的原纤维结合的局部结构。特别有趣的是局部金属协调与总体形态之间的关系。还已经表明，Abeta肽的组装是一个依赖成核的过程，它可以通过闪存冻结技术和/或物理分离来遵循该过程，从聚合成核通过原纤维形成传播。