Department of Neurochemistry, Tohoku University Graduate School of Medicine, Seiryo-cho, Aoba-ku, Sendai, 980-8575, Japan.
Cell Tissue Res. 2023 Apr;392(1):349-365. doi: 10.1007/s00441-022-03604-1. Epub 2022 Mar 21.
Prion diseases, also known as transmissible spongiform encephalopathies, are caused by the accumulation of abnormal isoforms of the prion protein (scrapie isoform of the prion protein, PrPSc) in the central nervous system. Many compounds with anti-prion activities have been found using in silico screening, in vitro models, persistently prion-infected cell models, and prion-infected rodent models. Some of these compounds include several types of polymers. Although the inhibition or removal of PrPSc production is the main target of therapy, the unique features of prions, namely protein aggregation and assembly accompanied by steric structural transformation, may require different strategies for the development of anti-prion drugs than those for conventional therapeutics targeting enzyme inhibition, agonist ligands, or modulation of signaling. In this paper, we first overview the history of the application of polymers to prion disease research. Next, we describe the characteristics of each type of polymer with anti-prion activity. Finally, we discuss the common features of these polymers. Although drug delivery of these polymers to the brain is a challenge, they are useful not only as leads for therapeutic drugs but also as tools to explore the structure of PrPSc and are indispensable for prion disease research.
朊病毒病，又称传染性海绵状脑病，是由朊病毒蛋白（瘙痒病朊病毒蛋白，PrPSc）在中枢神经系统中的异常异构体积累引起的。已经使用计算机筛选、体外模型、持续感染朊病毒的细胞模型和感染朊病毒的啮齿动物模型发现了许多具有抗朊病毒活性的化合物。这些化合物包括几种类型的聚合物。尽管抑制或去除 PrPSc 的产生是治疗的主要目标，但朊病毒的独特特征，即蛋白质聚集和组装伴随着空间结构的转变，可能需要针对抗朊病毒药物的不同策略，而不是针对传统的针对酶抑制、激动剂配体或信号转导调节的治疗药物。在本文中，我们首先概述了聚合物在朊病毒病研究中的应用历史。接下来，我们描述了每种具有抗朊病毒活性的聚合物的特征。最后，我们讨论了这些聚合物的共同特征。尽管将这些聚合物递送到大脑中是一个挑战，但它们不仅可用作治疗药物的先导，还可用作探索 PrPSc 结构的工具，是朊病毒病研究不可或缺的。
