XAS IMAGING OF DROSOPHILA MODELS OF NEURODEGENERATIVE DISEASE

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。 人类神经退行性疾病，例如阿尔茨海默氏病，影响着全世界超过 2000 万人，是西方社会成年人死亡的第四大原因和残疾的主要原因。这种新颖的研究人员合作将生物医学、基础科学和结构科学结合在一起。我们的团队拥有独特的优势，可以利用加拿大光源同步加速器和斯坦福同步加速器辐射实验室的力量与果蝇的遗传力量来识别神经变性过程中发生的化学和细胞变化。使用我们的技术只能可视化非常小的动物。果蝇是理想的选择，因为阿尔茨海默病和帕金森病的大脑病理可以在果蝇中重现。 此外，苍蝇对治疗帕金森病的药物有反应。使用已建立的神经退行性变苍蝇模型，我们将识别和量化大脑中的铁、锌、锰和铜，如果它们积累，我们将使用 X 射线吸收光谱成像将它们定位到特定的大脑区域。同步加速器还使我们能够确定这些金属的异常或有毒化学形式是否与神经退行性疾病有关。我们还将研究金属如何随着时间的推移而积累，以及它们在大脑中的位置如何与疾病进展和细胞病理学相关。最后我们将确定哪些治疗药物可以减少或防止有毒金属在大脑中的积累。这项工作将转化为用于药物功效测试的新测定系统，并可能通过识别哪些金属以及金属的哪些化学形式出现在阿尔茨海默病和帕金森病的早期来实现更好的早期诊断。

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. Human neurodegenerative diseases, such as Alzheimer's disease, affect more than 20 million people worldwide and represent the fourth leading cause of death and a major cause of disability amongst adults in Western societies. This novel partnership of investigators brings together the biomedical, basic and structural sciences. Our team is uniquely positioned to harness the power of the Canadian Light Source synchrotron and Stanford Synchrotron Radiation Laboratories to the genetic power of Drosophila to identify chemical and cellular changes occurring during neurodegeneration. Only very small animals can be visualized using our techniques. The fruitfly is ideal because brain pathology seen in Alzheimer's disease and Parkinson's disease can be reproduced in the fly. Furthermore, flies respond to drugs used to treat Parkinson's disease. Using established fly models of neurodegeneration, we will identify and quantify iron, zinc, manganese and copper in the brain and if they accumulate we will localize them to specific brain regions using x-ray absorption spectroscopy imaging. The synchrotron also enables us to determine if unusual or toxic chemical forms of these metals are associated with neurodegeneration. We will also investigate how metals accumulate over time and how this along with their location in the brain relates to disease progression and cellular pathology. Finally we will determine which therapeutic drugs can reduce or prevent the accumulation of toxic metals in the brain. This work will translate into new assay systems for drug efficacy testing and may lead to better early diagnosis by identifying which metals and which chemical forms of a metal appear early in Alzheimer's and Parkinson's disease.