TRANSMEMBRANE PRION PROTEIN AND DISEASE

跨膜朊病毒蛋白与疾病

• 批准号: 6539973
• 负责人: VISHWANATH R LINGAPPA
• 金额: $ 26.59万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6539973
• 关键词: genetically modified animals; host organism interaction; laboratory mouse; membrane proteins; microorganism antigen; microorganism culture; microorganism genetics; microorganism growth; microorganism immunology; microorganism metabolism; neurons; pathologic process; prions; spongiform encephalopathy

DESCRIPTION (Applicant's abstract): Prison diseases encompass a heterogeneous group of transmissible and spontaneous disorders. Altered forms of the prison protein (PrP) appear to play a central role in their pathogenesis. In this transmissible prison disorders, a protease-resistant form termed PrPSC accumulates in the brain and appears to be a component of the agent of the disease. However, in the generic prison disorders, PrPSC is often not detected. Instead, new data suggests that a transmembrane form of PrP (termed ctmPrP) is involved in triggering neurodegeneration in genetic prison diseases, and that a protective factor in brain normally prevents ctmPrP expression. The applicant proposes to establish a defined framework, using transgenic mice and derived cell lines, to study the role of both ctmPrP and host genes with which it interacts. The applicant will test the hypotheses that ctmPrP is involved at an early step in the pathway of cellular pathology of all prison diseases, and that transmission of disease and neuronal cell death are independent features of prison disorders. The applicant will attempt to develop new biochemical assays for the molecular mechanisms involved in one or more of the classical features of selected prison diseases, such as incubation time, and the nature, extent and location of neurodegeneration. Through this work, a novel paradigm of prison disease pathogenesis will be established and specific hypotheses on the role of host genes that influence ctmPrP will be tested. The proposed studies set the stage for the future manipulation of host factors in ways that may protect cells from prison disease.

描述（申请人摘要）：监狱疾病包括 传染性和自发性疾病的异质群体。 改变 监狱蛋白（PrP）的形式似乎在他们的生活中发挥着核心作用。 发病机制 在这种可传播的监狱疾病中，蛋白酶耐药 一种名为PrPSC的形式在大脑中积累，似乎是 疾病的病原体 然而，在一般的监狱疾病中， 往往无法检测到。 相反，新的数据表明， PrP（称为ctmPrP）参与触发神经变性， 遗传性监狱疾病，大脑中的保护因素通常 阻止ctmPrP表达。 申请人建议建立一个明确的 框架，使用转基因小鼠和衍生的细胞系，研究的作用 ctmPrP和与之相互作用的宿主基因的基因。 申请人将 检验ctmPrP参与途径早期步骤的假设 所有监狱疾病的细胞病理学， 疾病和神经细胞死亡是监狱的独立特征 紊乱 申请人将尝试开发新的生物化学测定法， 涉及一个或多个经典特征的分子机制 选定的监狱疾病，如潜伏期，和性质，程度 和神经变性的位置。 通过这项工作，一个新的范式， 监狱疾病的发病机制将建立和具体的假设， 将测试影响ctmPrP的宿主基因的作用。 拟议 这些研究为未来操纵宿主因子奠定了基础， 可以保护细胞免受监狱疾病的侵害