METAL IONS AND PROTEIN STRUCTURE IN ALZHEIMER'S DISEASE

这个子项目是许多利用 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。 阿尔茨海默病（AD）是一种神经退行性疾病，其涉及正常蛋白质的错误折叠  名为Abeta  在大脑中，最近与金属离子的结合有关。 据认为，金属不平衡涉及蛋白质错误折叠，并导致氧化损伤和神经元变性。 然而，这些金属离子和错误折叠的蛋白质在疾病过程中的功能还没有得到很好的理解。 最近，我们使用X射线荧光（XRF）微探针检查了严重AD病例的人脑组织，发现AD组织中含有锌和铜的“热点”。 我们还使用同步辐射FTIR显微光谱成像的二级结构的错误折叠的Abeta蛋白。有趣的是，这些热点与Abeta“淀粉样斑块”共定位，表明金属离子与AD中的淀粉样蛋白形成相关。 然而，随着疾病的进展，斑块形成和金属积累在AD病理学中的作用仍然不清楚。

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. Alzheimer's disease (AD) is a neurodegenerative disease that involves the misfolding of a normal protein  called Abeta  in the brain, which has recently been associated with the binding of metal ions. It is thought that metal imbalance is involved in protein misfolding and leads to oxidative damage and neuron degeneration. Yet, the functions of these metal ions and the misfolded proteins in the disease process are not well understood. Recently, we examined human brain tissue from severe AD cases using x-ray fluorescence (XRF) microprobe and found that AD tissue contains "hot spots" of zinc and copper. We also used synchrotron FTIR micro-spectroscopy to image the secondary structure of the misfolded Abeta protein. Interestingly, these hot spots are co-localized with Abeta "amyloid plaques", indicating an association of metal ions with amyloid formation in AD. However, the role of plaque formation and metal accumulation in the pathology of AD as the disease progresses is still not clear.