MOLECULAR PATHOLOGY OF CREUTZFELDT-JACOB DISEASE

克雅氏病的分子病理学

• 批准号: 2268474
• 负责人: Michael Gordon Harrington
• 金额: $ 20.18万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 1997-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2268474
• 关键词: biomarker; brain disorder diagnosis; cerebrospinal fluid; gel electrophoresis; human tissue; molecular pathology; nerve /myelin protein; spongiform encephalopathy

DESCRIPTION (Investigator's Abstract): The broad aim is to develop a diagnostic approach for Creutzfeldt-Jakob disease (GJD), based on characterization of disease-associated cerebrospinal fluid (CSfl proteins. This will be achieved by direct comparison to reference maps of normal cSF proteins, and will also include a measure of each patient's specific pathology. The underlying hypothesis is that a) there is a unique distribution of proteins for each body fluid, cell type and tissue that can, like a fingerprint, provide a reference map that is specific for each fluid, cell type or tissue; b) damage to the nervous system will lead to addition of disease-associated proteins that are distinct from the normal CSF proteins; c) those diagnostic proteins not found in normal CSF will reveal the source(s) when they are found in the reference maps of other cells, tissues or body fluids; d) the identified source of disease-associated proteins will provide interpretation of the cellular and molecular pathology in each patient. Specifically, common reference maps will be made from normal "volunteers" for CSF plasma, red and white blood cells and brain tissue. Such maps will be compared from the 1000-5000 protein spots of high resolution two dimensional electrophoretic gel patterns of each sample. Experiments on multiple gels of the same sample and separate cohorts for each sample group will define the technical and biological variations. Extra proteins in the CSF from patients with will then be identified by comparison with the normal CSF map. These additional associated CSF proteins will be compared to the other fluid, cell and brain tissue maps to identify their protein source. Proteins that distinguish the patients with will be further characterized by partial amino acid sequence analysis and peptide mapping, both to establish their molecular identity and to enable more detailed investigation of individual proteins. The results of this study should indicate the utility of this approach for other human disease.

描述（研究者摘要）：总体目标是开发一种 克雅氏病 (GJD) 的诊断方法 疾病相关脑脊液 (CSfl 蛋白质。 这将通过与参考地图的直接比较来实现 正常 cSF 蛋白，并且还将包括每个的测量 患者的具体病理。基本假设是 a) 每种体液、细胞类型和蛋白质的独特分布 可以像指纹一样提供参考图的组织 针对每种液体、细胞类型或组织； b) 神经损伤 系统将导致添加与疾病相关的蛋白质 与正常脑脊液蛋白不同； c) 那些诊断蛋白不 当在正常脑脊液中发现时，将揭示其来源 其他细胞、组织或体液的参考图； d) 已确定的 疾病相关蛋白的来源将提供对 每个患者的细胞和分子病理学。 具体来说，常见的 参考图将由正常“志愿者”制作脑脊液血浆，红色 以及白细胞和脑组织。此类地图将从 高分辨率二维1000-5000个蛋白质点 每个样品的电泳凝胶图案。多种凝胶的实验 相同样本和每个样本组的单独队列将 定义技术和生物学差异。额外的蛋白质 然后通过与患者的脑脊液比较来识别 正常脑脊液图。这些额外的相关 CSF 蛋白将 与其他液体、细胞和脑组织图谱进行比较以识别 他们的蛋白质来源。区分患者意志的蛋白质 通过部分氨基酸序列分析进一步表征和 肽图谱，既可以确定其分子身份，也可以 能够对单个蛋白质进行更详细的研究。结果 这项研究的结果应该表明这种方法对于其他人的效用 人类疾病。