Molecular mechanism and therapeutic implications of prion disease strain types in sporadic Creutzfeldt Jakob Disease.

朊病毒病是一组影响人类和动物的传染性神经退行性疾病。人类最常见的形式是散发性克雅氏病（CJD），尽管也存在获得性（变异型CJD）和遗传性（家族性CJD）形式。朊病毒疾病可通过接种或饮食接触受感染的组织传播。这种被称为朊病毒的传染因子尚未得到最终鉴定。然而，纯化朊病毒的主要成分是宿主朊病毒蛋白的异常疾病相关形式。散发性克雅氏病病程和病理学的差异提示该病可能由不同的朊病毒株引起。不同朊病毒株的存在可以解释在朊病毒疾病的啮齿动物模型中建模的抗朊病毒疗法的有限临床成功。在这项研究中，朊病毒繁殖的无细胞模型将被用来研究人类朊病毒株的基础。该测定也将用于鉴定和确定抗朊病毒化合物的治疗功效是否受人朊病毒菌株类型的影响。本研究将代表抗朊病毒治疗的第一个宿主物种和朊病毒株特异性筛选，旨在开发用于鉴定和开发人类朊病毒疾病治疗的最佳可能模型。

The prion diseases are a group of transmissible, neurodegenerative disorders affecting both humans and animals. The most common form in humans is sporadic Creutzfeldt-Jakob disease (CJD), although acquired (variant CJD) and inherited (familial CJD) forms also exist. Prion diseases are transmissible by inoculation with, or dietary exposure to, infected tissues. The infectious agent, referred to as a prion , has not been conclusively identified. However, a major component of purified prions is an abnormal disease associated form of the host prion protein. Differences in the duration of illness and pathology of sporadic CJD suggests that the disease may be caused by different prion strains. The existence of different prion strains may explain the limited clinical success of anti-prion therapeutics modeled in rodent models of prion diseases. In this study a cell-free model of prion propagation will be used to investigate the basis of human prion strains. This assay will also be used to identify and determine whether the therapeutic efficacy of anti-prion compounds is influenced by human prion strain type. This study will represent the first host species and prion strain specific screen of anti-prion therapeutics aimed at developing the best possible model for the identification and development of therapeutics for human prion diseases.