XAS IMAGING OF DROSOPHILA MODELS OF NEURODEGENERATIVE DISEASE

果蝇神经退行性疾病模型的 XAS 成像

• 批准号: 7721900
• 负责人: HELEN NICHOL
• 金额: $ 1.38万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721900
• 关键词: Adult; Affect; Alzheimer' s Disease; Animals; Biological Assay; Brain; Brain Pathology; Brain region; Cause of Death; Chemicals; Computer Retrieval of Information on Scientific Projects Database; Copper; Disease Progression; Drosophila genus; Drug usage; Early Diagnosis; Funding; Genetic; Grant; Human; Image; Institution; Iron; Laboratories; Lead; Light; Localized; Location; Manganese; Metals; Modeling; Nerve Degeneration; Neurodegenerative Disorders; Parkinson Disease; Pharmaceutical Preparations; Poison; Positioning Attribute; Research; Research Personnel; Resources; Science; Societies; Source; Spectrum Analysis; Synchrotrons; System; Techniques; Testing; Therapeutic; Time; Translating; United States National Institutes of Health; Work; Zinc; absorption; cellular pathology; disability; drug efficacy; fly; novel; prevent; synchrotron radiation; toxic metal

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.

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。 人类神经退行性疾病，如阿尔茨海默病，影响着全球2000多万人，是西方社会成年人死亡的第四大原因和致残的主要原因。这种新的研究伙伴关系将生物医学、基础科学和结构科学结合在一起。我们的团队具有得天独厚的优势，能够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，利用果蝇的遗传力量来识别神经退化过程中发生的化学和细胞变化。只有非常小的动物才能用我们的技术可视化。果蝇是理想的，因为阿尔茨海默病和帕金森病的大脑病理可以在果蝇身上复制。此外，苍蝇对治疗帕金森氏症的药物也有反应。使用已建立的神经退行性变的苍蝇模型，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的化学形式是否与神经退化有关。我们还将研究金属如何随着时间的推移积累，以及这与它们在大脑中的位置如何与疾病进展和细胞病理有关。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聚。这项工作将转化为新的药效测试系统，并可能通过识别哪些金属和哪些金属的化学形态在阿尔茨海默氏症和帕金森氏病中出现得较早，从而实现更好的早期诊断。