XAS IMAGING OF DROSOPHILA MODELS OF NEURODEGENERATIVE DISEASE

这个子项目是许多研究子项目中的一个 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来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 人类神经退行性疾病，如阿尔茨海默病，影响全世界超过2000万人，并且代表西方社会成人中的第四大死亡原因和主要残疾原因。这种新型的研究伙伴关系汇集了生物医学，基础和结构科学。我们的团队具有独特的优势，可以利用加拿大光源同步加速器和斯坦福大学同步辐射实验室的力量来研究果蝇的遗传力量，以确定神经变性过程中发生的化学和细胞变化。只有非常小的动物可以使用我们的技术可视化。果蝇是理想的，因为在阿尔茨海默病和帕金森病中看到的大脑病理可以在果蝇中重现。 此外，苍蝇对用于治疗帕金森病的药物有反应。使用已建立的神经变性苍蝇模型，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不寻常或有毒化学形式是否与神经变性有关。我们还将研究金属如何随着时间的推移而积累，以及这沿着它们在大脑中的位置与疾病进展和细胞病理学的关系。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疗效测试的新的分析系统，并可能通过识别哪些金属和金属的化学形式在阿尔茨海默病和帕金森病早期出现而导致更好的早期诊断。

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.