Structures and Activities of Prions and Prion Proteins

朊病毒和朊病毒蛋白的结构和活性

• 批准号: 8745318
• 负责人: BYRON CAUGHEY
• 金额: $ 52.48万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8745318
• 关键词: Architecture; Biochemical; Bovine Spongiform Encephalopathy; Chronic Wasting Disease; Creutzfeldt-Jakob Syndrome; Data; Development; Disease; Electrons; Experimental Autoimmune Encephalomyelitis; Goals; Lead; Ligands; Microscopic; Modeling; Molecular; Mus; Neurodegenerative Disorders; Pathogenesis; Prion Diseases; Prions; Publishing; Reporting; Role; Scrapie; Structure; Toll-like receptors; Work; base; beta pleated sheet; disease transmission; response; transmission process

In FY2013: 1) We have worked toward a better understanding of prion structure by initiating the application of new (to our lab) biochemical, immunological, spectroscopic, electron microscopic, and computational approaches to defining the structure of infectious prions. We have developed new models of prion structure is being built and evaluated based on our own new data, as well as published reports. These models are based on parallel-in-register beta sheet architectures, partial versions of which have been proposed by others. These developments are in progress and are expected to lead to significant discoveries soon. 2) We have assessed the role of normal prion protein in responses to stimulators of toll-like receptor ligands and have not found any significant effects. 3) We have probed the role of normal prion protein in the experimental autoimmune encephalomyelitis in mice of the C57/BL background and found no significant effect.

2013 财年：1) 我们开始应用新的（对我们实验室而言）生化、免疫学、光谱、电子显微镜和计算方法来定义传染性朊病毒的结构，从而更好地了解朊病毒的结构。我们已经开发了新的朊病毒结构模型，正在根据我们自己的新数据以及已发表的报告进行构建和评估。这些模型基于并行寄存器 beta 表架构，其部分版本已由其他人提出。这些进展正在进行中，预计很快就会带来重大发现。 2）我们评估了正常朊病毒蛋白在Toll样受体配体刺激物反应中的作用，但没有发现任何显着影响。 3）我们在C57/BL背景的小鼠实验性自身免疫性脑脊髓炎中探讨了正常朊病毒蛋白的作用，没有发现明显的作用。