METAL IONS AND PROTEIN STRUCTURE IN ALZHEIMER'S DISEASE

阿尔茨海默病中的金属离子和蛋白质结构

• 批准号: 7954902
• 负责人: LISA M MILLER
• 金额: $ 2.61万
• 依托单位: ILLINOIS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954902
• 关键词: Affect; Alzheimer' s Disease; Amyloid; Amyloid beta-Protein; Biochemical; Biophysics; Biopsy; Central Nervous System Diseases; Computer Retrieval of Information on Scientific Projects Database; Copper; Disease; Disease Progression; Early Diagnosis; Eye; Funding; Goals; Grant; Homeostasis; Image; Institution; Ions; Kidney; Liver; Metal Ion Binding; Metals; Nerve Degeneration; Neurodegenerative Disorders; Neurons; Organ; Pancreas; Process; Research; Research Personnel; Resources; Role; Source; Spleen; Staging; Staining method; Stains; Synchrotrons; Systemic disease; Time; Tissues; Trace metal; United States National Institutes of Health; Zinc; brain tissue; mouse model; oxidative damage; pre-clinical; protein structure

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. Alzheimer's disease (AD) is a neurodegenerative disorder that involves the misfolding of a naturally occurring protein, amyloid beta (Abeta), which has recently been associated with the binding of metal ions such as copper and zinc (Miller, 2006). Disturbance of metal homeostasis is believed to be involved in the misfolding process, leading to oxidative damage and the degeneration of neurons. Although this disease is generally considered a central nervous system (CNS) disorder, accumulating evidence suggested the involvement of non-neuronal organs, such as the eyes, pancreas, spleen or liver, during the course of the disease. These findings suggest that AD may be a systemic disease and perhaps biopsies of these tissues may provide a means for early diagnosis and treatment. However, the roles of Abeta, trace metals, and other biochemical changes in non-neuronal tissue during disease progression are still far from being understood. Therefore, the goal of this proposal is to study tissues from amyloid-affected organs including the eye, kidney, liver and spleen in a mouse model of AD. We will use using synchrotron XRF microprobe to image trace metal composition and distribution in the tissue at different time points during the disease, from pre-clinical stage to terminally diseased. These results will be compared with our findings from brain tissue and correlated with conventional histological staining and synchrotron infrared imaging (at NSLS), in order to understand the systemic relationship between metal distribution/accumulation and organic biochemical changes in the affected organs.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 阿尔茨海默氏病（AD）是一种神经退行性疾病，涉及对天然存在的蛋白质淀粉样蛋白β（ABETA）的错误折叠，最近与金属离子（如铜和锌）的结合有关（Miller，2006）。据信金属体内平衡的扰动参与了错误折叠的过程，导致氧化损伤和神经元的变性。尽管该疾病通常被认为是一种中枢神经系统（CNS）疾病，但积累的证据表明在疾病过程中，非神经元器官（例如眼睛，胰腺，脾或肝脏）的参与。这些发现表明AD可能是一种全身性疾病，也许这些组织的活检可能为早期诊断和治疗提供一种手段。然而，疾病进展过程中非神经组织的Abeta，微量金属和其他生化变化的作用仍然远非被理解。因此，该提案的目的是研究AD小鼠模型中受淀粉样蛋白影响器官，包括眼睛，肾脏，肝脏和脾脏在内的组织。我们将使用Synchrotron XRF微探针在疾病期间在不同时间点（从临床前阶段到绝症）在组织中的痕量金属组成和分布。这些结果将与我们来自脑组织的发现进行比较，并与常规的组织学染色和同步红外成像（在NSLS）相关，以了解金属分布/积累与受影响器官的有机生化变化之间的全身关系。