How do glycosaminoglycans promote the propagation of prions?

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），尽管获得性（变异型CJD）和遗传性（家族性CJD）形式也被认可。朊病毒疾病可以通过接种或饮食接触受感染的组织而传播给同一物种。感染因子，称为朊病毒，尚未在分子水平上确定。然而，纯化的朊病毒的主要成分是宿主编码的朊病毒蛋白的异常疾病相关形式。了解疾病相关形式的朊病毒蛋白是如何产生的，以及宿主衍生的辅因子如何促进其形成，将有助于我们了解这些疾病的感染性，并制定有效的治疗和预防策略。糖胺聚糖是细胞外基质的宿主来源组分，其与在患有朊病毒疾病的患者的脑组织中发现的朊病毒蛋白斑块相关。糖胺聚糖被认为影响朊病毒的传播和传染性的持续传播。在这项研究中，糖胺聚糖在疾病相关朊病毒蛋白的形成和感染性的产生中的重要性将使用无细胞和基于细胞的朊病毒传播模型进行研究。从本研究中获得的理解将用于开发一种高通量测定法，该测定法可用于在临床疾病发展之前和治疗干预可能有效的时间范围内检测朊病毒感染。

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 are recognised. Prion diseases are transmissible to the same species by inoculation with, or dietary exposure to, infected tissues. The infectious agent, referred to as a prion , has not been identified at the molecular level. However, a major component of purified prions is an abnormal disease associated form of the host encoded prion protein. Understanding how the disease associated form of the prion protein is generated and how host-derived cofactors contribute to its formation will help in our understanding of the infectious nature of these diseases and in the development of effective therapeutic and prophylactic strategies. Glycosaminoglycans are host-derived components of the extracellular matrix that are associated with prion protein plaques found in the brain tissue of patients with prion diseases. Glycosaminoglycans are believed to influence the transmission of prions and the ongoing propagation of infectivity. In this study the importance of glycosaminoglycans in the formation of the disease associated prion protein and the generation of infectivity will be investigated using both cell-free and cell-based models of prion propagation. The understanding gained from this study will be used to develop a high throughput assay that can be used to detect prion infection prior to the development of clinical disease and within a time frame whereby therapeutic intervention may be effective.