METAL IONS AND PROTEIN STRUCTURE IN ALZHEIMER'S DISEASE

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。 锌、铜、铁等金属离子在正常情况下存在于大脑中，但在阿尔茨海默病中，人们认为金属离子失衡会导致A？聚集，从而导致氧化损伤和神经元退化。海马体是阿尔茨海默病的关键区域，已有证据表明阿尔茨海默病的金属失衡。例如，Deibel和他的同事[3]发现AD患者海马体中铜的含量减少，而锌和铁的含量增加。此外，在人类AD患者和转基因小鼠的海马区，还观察到了锌转运蛋白ZnT3、ZnT4和ZnT6的高表达。 尽管海马体中的金属动态平衡似乎在阿尔茨海默病中至关重要，但海马体特定区域的金属含量如何随着时间的推移而变化仍有待确定。因此，我们使用XRF微探针检测了PSAPP模型AD小鼠(N=20)和对照组(CNT，N=20)小鼠海马铜、铁和锌的含量随年龄的变化。我们假设PSAPP小鼠的海马区金属离子含量会随着年龄的增长而发生变化，而CNT小鼠的海马区金属离子含量将保持不变。

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. Metal ions of zinc (Zn), copper (Cu), and iron (Fe) are present in the brain under normal conditions, but in AD it is thought that metal imbalances contribute to A¿ aggregation leading to oxidative damage and neuron degeneration. The hippocampus, a critical region affected by AD, has shown evidence of metal imbalance in AD. For example, Deibel and colleagues [3] found a decrease in Cu, and an increase in Zn and Fe in the hippocampus in AD. In addition, elevated expression of Zn transporter proteins ZnT3, ZnT4, and ZnT6 have been observed in the hippocampi of human AD patients and transgenic mice. Though metal homeostasis in the hippocampus appears to be critical in AD, how metal content in specific regions of the hippocampus changes over time remains to be determined. Thus, we examined the Cu, Fe, and Zn content the hippocampus of the PSAPP mouse model of AD (N = 20) and in control (CNT, N = 20) mice as a function of age using XRF microprobe. We hypothesized that PSAPP mice will show changes in hippocampal metal ion content as the mice age, while the content in CNT mice will remain constant.