XAS IMAGING OF DROSOPHILA MODELS OF NEURODEGENERATIVE DISEASE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，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2 000多万人，是西方社会成年人第四大死因和主要致残原因。这种新颖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同步加速器辐射实验室的力量来研究果蝇的遗传能力，以识别神经变性过程中发生的化学和细胞变化。只有非常小的动物才能使用我们的技术进行可视化。果蝇是理想的选择，因为阿尔茨海默病和帕金森病的脑部病理可以在果蝇身上重现。此外，果蝇对治疗帕金森氏症的药物有反应。利用已建立的苍蝇神经变性模型，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。同步加速器还能让我们确定这些金属的异常或有毒化学形式是否与神经变性有关。我们还将研究金属是如何随着时间的推移而积累的，以及它们在大脑中的位置与疾病进展和细胞病理的关系。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。这项工作将转化为药物功效测试的新分析系统，并可能通过识别阿尔茨海默病和帕金森病早期出现的金属和金属的化学形式来更好地进行早期诊断。

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.