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

Prion病是一组可传播的神经退行性疾病，对人类和动物都有影响。人类最常见的形式是散发性克雅氏病(CJD)，但也存在获得性(变异型CJD)和遗传性(家族性CJD)。通过接种受感染的组织或通过饮食接触到受感染的组织，Pron疾病是可以传播的。被称为普里恩的感染性病原体尚未确定。然而，纯化的Prion的一个主要成分是宿主Prion蛋白的一种不正常的疾病相关形式。散发性CJD的病程和病理差异提示该病可能是由不同的普恩病毒株引起的。不同的Prion菌株的存在可能解释了在Pron疾病的啮齿动物模型中建立的反Prion治疗方法的临床成功有限的原因。在这项研究中，将使用一个无细胞的Pron繁殖模型来研究人类Pron菌株的基础。这项试验还将用于鉴定和确定抗普鲁恩化合物的治疗效果是否受人类普恩病毒株类型的影响。这项研究将代表第一个宿主种类和Prion菌株特异性的抗Prion治疗药物的筛选，目的是为人类Prion疾病的治疗药物的鉴定和开发开发最好的可能模型。

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.