Despite being caused by a single protein, prion diseases are strikingly heterogenous. Individual prion variants, known as strains, possess distinct biochemical properties, form aggregates with characteristic morphologies and preferentially seed certain brain regions, causing markedly different disease phenotypes. Strain diversity is determined by protein structure, post-translational modifications and the presence of extracellular matrix components, with single amino acid substitutions or altered protein glycosylation exerting dramatic effects. Here, we review recent advances in the study of prion strains and discuss how a deeper knowledge of the molecular origins of strain heterogeneity is providing a foundation for the development of anti-prion therapeutics.

尽管由单一蛋白质引起，但朊病毒疾病具有惊人的异质性。单个朊病毒变体，称为菌株，具有独特的生化特性，形成具有特征形态的聚集体，并优先播种某些大脑区域，导致明显不同的疾病表型。菌株多样性由蛋白质结构、翻译后修饰和细胞外基质成分的存在决定，单个氨基酸取代或改变的蛋白质糖基化产生显着影响。在这里，我们回顾了朊病毒菌株研究的最新进展，并讨论了对菌株异质性分子起源的更深入了解如何为开发抗朊病毒疗法奠定基础。