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.

可传播的海绵状脑病（TSE或PRION疾病）是致命的不可治疗的神经退行性疾病，例如Crapie，Creutzfeldt-Jakob病（CJD），牛spongine Spongiorment spongiorment Chiormanty和慢性浪费疾病（CWD）。 TSE发病机理涉及被感染宿主中称为PRPRE的异常蛋白的积累。我们先前已经鉴定出硫酸化聚糖和磷酸硫酸盐寡核苷酸是有效的抗植物化合物，可有效抑制PRPRES的积累，放缓或阻止实验动物中刮饼的进展。在这个财政年度，我们使用核磁共振，圆形二分法，荧光极化和红外光谱法扩展了这些类型的抑制剂与重组prion蛋白结合的研究。发现戊糖基多硫酸盐可以在PRP的八肽重复区域稳定结构。