XAS INVESTIGATION OF ALZHEIMER'S BETA-AMYLOID FIBRILS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们建议使用X-射线吸收光谱来表征参与淀粉样纤维形成的重金属位点（Zn（II）和Cu（II））。Zn（II）和Cu（II）已成为淀粉样蛋白β（Abeta）肽聚集和该过程的神经毒性的重要因素。我们建议调查的本地结构的Zn（II）和Cu（II）结合到原纤维形成的一些截短的Abeta肽在体外。特别感兴趣的是局部金属配位和聚集体形态之间的关系。还已经表明，Abeta肽的组装是成核依赖性过程，这将允许我们通过快速冷冻技术和/或物理分离，从聚集体成核到原纤维形成的传播，随时间推移跟踪该过程。

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.