XAS INVESTIGATION OF ALZHEIMER'S BETA-AMYLOID FIBRILS

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 我们建议使用 X 射线吸收光谱来表征淀粉样原纤维形成中涉及的重金属位点（Zn(II) 和 Cu(II)）。 Zn(II) 和 Cu(II) 已成为淀粉样β (Abeta) 肽聚集以及该过程的神经毒性的重要因素。我们建议在体外研究 Zn(II) 和 Cu(II) 与许多截短的 Abeta 肽形成的原纤维结合的局部结构。特别令人感兴趣的是局部金属配位和聚集体形态之间的关系。还表明，Abeta 肽的组装是一个依赖成核的过程，这将使我们能够通过闪冻技术和/或物理分离，随着时间的推移跟踪该过程，从聚集成核到原纤维形成的传播。

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.