XAS STUDIES OF ALPHA-SYNUCLEIN

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。 α-突触核蛋白(α-syn)与许多神经退行性疾病的发病机制有关，其中最著名的是帕金森-S病(PD)。散发性帕金森病与促进氧化应激和异常氧化还原活性金属代谢的环境因素有关，在体外观察到了金属增强的α-SYN寡聚作用。Lee实验室最近的工作表明，铜(II)离子加速聚集，铜离子被结合到α-SYN中，在N-末端附近有最紧密的亲和力结合(基于电感耦合等离子体质谱和荧光猝灭)。正在进行铜K-EDGE和EXAFS研究，以检查WT蛋白和相关突变体中铜结合位点的局部结构。在SSRL BL9-3上测量的初步数据表明，可以获得低至100微摩尔的铜浓度的EXAFS数据。

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. Alpha-Synuclein (alpha-syn) has been implicated in the pathogenesis of a number of neurodegenerative diseases, the best known of which is Parkinson?s disease (PD). The sporadic form of PD has been linked to environmental factors that promote oxidative stress and aberrant redox-active metal metabolism, and metal-enhanced oligomerization of alpha-syn has been observed in vitro. Recent work in the Lee laboratory has shown that Cu(II) ions accelerate aggregation and that the copper ions are incorporated into alpha-syn, with the tightest affinity binding near the N-terminus (based on ICP-MS and fluorescence quenching). Cu K-edge and EXAFS studies are being pursued to examine the local structure of the Cu binding site in the WT protein and in related mutants. Preliminary data measured on SSRL BL9-3 have shown that EXAFS data can be obtained for copper concentrations as low as 100 micromolar.