XAS INVESTIGATION OF ALZHEIMER'S BETA-AMYLOID FIBRILS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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置(锌(II)和铜(II))。锌(II)和铜(II)是淀粉样β蛋白(Abeta)多肽聚集及其神经毒性的重要因素。我们建议在体外研究锌(II)和铜(II)与一些截短的Abeta多肽形成的纤维结合的局部结构。特别感兴趣的是局部金属配位与聚集形态之间的关系。研究还表明，Abeta多肽的组装是一个依赖于成核的过程，这将使我们能够通过闪速冷冻技术和/或物理分离，随着时间的推移跟踪这一过程，从聚集成核到纤维形成的传播。

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.