Prion Disease Therapeutics

朊病毒病治疗

• 批准号: 8157073
• 负责人: BYRON CAUGHEY
• 金额: $ 2.31万
• 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/8157073
• 关键词: Binding; Chronic Wasting Disease; Disease; Phosphorothioate Oligonucleotide; Prion Diseases; Recombinants; Therapeutic; prevent

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 protein, called PrPres, in infected hosts. We have previously identified sulfated glycans and phosphorothioate oligonucleotides as potent anti-prion compounds that are effective in inhibiting PrPres accumulation and slowing or prevent the progression of scrapie in experimental animals. This fiscal year, we have extended our studies of the binding of these types of inhibitors to recombinant prion protein using nuclear magnetic resonance, circular dichroism, fluorescence polarization and infrared spectroscopy. Pentosan polysulfate was found to stabilize a structure in the octapeptide repeat region of PrP.

传染性海绵状脑病（tse或朊病毒疾病）是一种致命的无法治愈的神经退行性疾病，如痒病、克雅氏病（CJD）、牛海绵状脑病和慢性消耗性疾病（CWD）。TSE的发病机制涉及一种被称为PrPres的异常蛋白在被感染宿主体内的积累。在实验动物中，我们已经发现硫代聚糖和硫代寡核苷酸是有效的抗朊病毒化合物，可以有效地抑制PrPres的积累，减缓或防止痒病的进展。本财政年度，我们利用核磁共振、圆二色性、荧光偏振和红外光谱扩展了这些类型的抑制剂与重组朊病毒蛋白结合的研究。聚硫酸戊聚糖稳定了PrP的八肽重复区结构。