School of Biology and Environmental Science, University College Dublin, Belfield, Dublin, Ireland.
PLoS One. 2013;8(1):e55282. doi: 10.1371/journal.pone.0055282. Epub 2013 Jan 28.
Prion diseases, also known as transmissible spongiform encephalopathies, are a group of fatal neurodegenerative diseases that include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle and Creutzfeldt-Jakob disease (CJD) in humans. The 'protein only hypothesis' advocates that PrP(Sc), an abnormal isoform of the cellular protein PrP(C), is the main and possibly sole component of prion infectious agents. Currently, no effective therapy exists for these diseases at the symptomatic phase for either humans or animals, though a number of compounds have demonstrated the ability to eliminate PrPSc in cell culture models. Of particular interest are synthetic polymers known as dendrimers which possess the unique ability to eliminate PrP(Sc) in both an intracellular and in vitro setting. The efficacy and mode of action of the novel anti-prion dendrimer mPPIg5 was investigated through the creation of a number of innovative bio-assays based upon the scrapie cell assay. These assays were used to demonstrate that mPPIg5 is a highly effective anti-prion drug which acts, at least in part, through the inhibition of PrP(C) to PrP(Sc) conversion. Understanding how a drug works is a vital component in maximising its performance. By establishing the efficacy and method of action of mPPIg5, this study will help determine which drugs are most likely to enhance this effect and also aid the design of dendrimers with anti-prion capabilities for the future.
朊病毒病，又称传染性海绵状脑病，是一组致命的神经退行性疾病，包括绵羊的瘙痒病、牛的海绵状脑病（BSE）和人类的克雅氏病（CJD）。“蛋白质唯一假说”主张，PrP（Sc），即细胞蛋白 PrP（C）的异常同工型，是朊病毒感染因子的主要成分，可能是唯一成分。目前，无论是在人类还是动物的症状期，都没有有效的治疗方法，尽管一些化合物已证明在细胞培养模型中能够消除 PrPSc。特别引人关注的是合成聚合物，称为树突状聚合物，它们具有在细胞内和体外环境中消除 PrP（Sc）的独特能力。新型抗朊病毒树突聚合物 mPPIg5 的功效和作用机制是通过基于瘙痒病细胞测定法创建了许多创新的生物测定法来研究的。这些测定法用于证明 mPPIg5 是一种非常有效的抗朊病毒药物，至少部分通过抑制 PrP（C）转化为 PrP（Sc）起作用。了解药物的作用机制是最大限度发挥其性能的重要组成部分。通过确定 mPPIg5 的功效和作用机制，本研究将有助于确定哪些药物最有可能增强这种效果，并有助于为未来设计具有抗朊病毒能力的树突聚合物。
