Prion Disease Therapeutics

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的发病机制涉及一种称为PrPres的异常蛋白质在感染宿主中的积累。我们以前已经确定硫酸化聚糖和硫代磷酸寡核苷酸作为有效的抗朊病毒化合物，可有效抑制PrPres积累，减缓或预防实验动物瘙痒病的进展。本财政年度，我们扩大了我们的研究，这些类型的抑制剂的结合重组朊病毒蛋白使用核磁共振，圆二色性，荧光偏振和红外光谱。戊聚糖多硫酸酯被认为是稳定的八肽重复区的PrP的结构。

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.