Prion Disease Therapeutics

朊病毒病治疗

• 批准号: 8745518
• 负责人: BYRON CAUGHEY
• 金额: $ 13.12万
• 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/8745518
• 关键词: Amyloid; Animals; Bovine Spongiform Encephalopathy; Brazil; Characteristics; Chronic Wasting Disease; Creutzfeldt-Jakob Syndrome; Disease; Extramural Activities; Goals; Human; Libraries; Neurodegenerative Disorders; Pathogenesis; PrPSc Proteins; Prion Diseases; Prions; Research Personnel; Scrapie; Sheep; System; Testing; Therapeutic; Therapeutic Agents; amyloid formation; cervid; design; novel; novel therapeutics; protein misfolding; therapeutic target

The transmissible spongiform encephalopathies (TSEs or prion diseases)are fatal untreatable neurodegenerative diseases such as scrapie, Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy and chronic wasting disease (CWD). TSE pathogenesis involves the accumulation of an abnormal misfolded protein, called PrPres, in infected hosts. In FY 2013: 1) We have collaborated with extramural investigators to identify a designed Trpzip-3 β-hairpin that inhibits amyloid formation in two different amyloid systems. 2) We have continued to search for new anti-prion compounds from libraries of novel compounds that have been synthesized in Brazil by our collaborators. A number of new compounds have been identified that block PrP-res formation and have other attractive characteristics, but further testing of these compounds will be required to better establish their therapeutic potential.

传染性海绵状脑病（transmissible spongiform encephalopathies，TSE或prion diseases）是一种无法治愈的神经退行性疾病，如羊瘙痒病、克雅氏病（Creutzfeldt-Jakob disease，CJD）、牛海绵状脑病（bovine spongiform encephalopathy，BSE）和慢性消耗性疾病（chronic wasting disease，CWD）。TSE发病机制涉及在感染宿主中异常错误折叠蛋白质（称为PrPres）的积累。2013财年：1）我们与校外研究人员合作，确定了一种设计的Trpzip-3-发夹，可抑制两种不同淀粉样蛋白系统中的淀粉样蛋白形成。2)我们继续从我们的合作者在巴西合成的新化合物库中寻找新的抗朊病毒化合物。一些新的化合物已被确定，阻止PrP-res的形成，并具有其他有吸引力的特点，但这些化合物的进一步测试将需要更好地建立其治疗潜力。