Infectivity-associated PrP^Sc and disease duration-associated PrP^Sc of mouse BSE prions

SummaryDisease-related prion protein (PrP^Sc), which is a structural isoform of the host-encoded cellular prion protein, is thought to be a causative agent of transmissible spongiform encephalopathies. However, the specific role of PrP^Sc in prion pathogenesis and its relationship to infectivity remain controversial. A time-course study of prion-affected mice was conducted, which showed that the prion infectivity was not simply proportional to the amount of PrP^Sc in the brain. Centrifugation (20,000 ×<i>g</i>) of the brain homogenate showed that most of the PrP^Sc was precipitated into the pellet, and the supernatant contained only a slight amount of PrP^Sc. Interestingly, mice inoculated with the obtained supernatant showed incubation periods that were approximately 15 days longer than those of mice inoculated with the crude homogenate even though both inocula contained almost the same infectivity. Our results suggest that a small population of fine PrP^Sc may be responsible for prion infectivity and that large, aggregated PrP^Sc may contribute to determining prion disease duration.疾病相关朊蛋白（disease-related prion protein, PrP^Sc）是宿主编码的细胞朊蛋白的结构异构体，被认为是传染性海绵状脑病（transmissible spongiform encephalopathies）的致病因子。然而，PrP^Sc在朊病毒发病机制中的具体作用，及其与感染活性的关联仍存在争议。本研究对感染朊病毒的小鼠开展了时间进程研究，结果显示朊病毒的感染活性并非与脑中PrP^Sc的含量呈简单的线性正相关。对脑匀浆进行20000×g离心后，可见大部分PrP^Sc沉降至沉淀组分，而上清液中仅含微量PrP^Sc。值得注意的是，尽管两种接种物的感染活性几乎一致，但经上述上清液接种的小鼠，其潜伏期较经粗匀浆接种的小鼠延长了约15天。本研究结果提示，少量细小形态的PrP^Sc可能是朊病毒感染活性的核心介导因子，而大型聚集态的PrP^Sc则可能参与调控朊病毒病的病程时长。

搜集汇总

背景与挑战

背景概述

该数据集聚焦于小鼠BSE朊病毒中PrPSc蛋白的不同形态与传染性和疾病持续时间的关系。研究发现，朊病毒传染性并非简单与大脑中PrPSc总量成正比，而是由少量精细PrPSc驱动，而大聚集PrPSc可能影响疾病进程。数据集通过实验数据支持了PrPSc在朊病毒发病机制中的复杂角色，为相关领域提供了关键见解。