Pathophysiology of prion accumulation in skeletal muscle

Priori疾病同样影响人类和动物，导致致命的神经退行性疾病，被认为是由广泛表达的朊病毒蛋白的构象变化引起的。虽然朊病毒疾病仅在中枢神经系统引起形态学上可证实的损害，但非神经组织区室如淋巴器官和骨骼肌的损害是明显的。朊病毒疾病的一个子集，如自然绵羊瘙痒症、牛海绵状脑病、鹿和麋鹿的慢性消耗病以及人类的变异型克雅氏病，被认为是由外周暴露于朊病毒引起的。早在朊病毒在中枢神经系统中被发现之前，就有可能在非神经元部位（如淋巴网状系统或肌肉室）检测到朊病毒。朊病毒在肌肉间室中积累的基础事件至今仍是个谜。在这个建议中，我们的目标是确定因素，有助于朊病毒积累在这个车厢，集中在各种类型的细胞存在于这个小生境，如外周神经，淋巴造血细胞和myoctyes的贡献。

Priori diseases affect humans and animals likewise, leading to fatal neurodegenerative diseases that are thought to be caused by a conformational change in the widely expressed prion protein. Although prion diseases cause morphologically demonstrable damage only in the central nervous system, involvement of non neural tissue compartments such as lymphoid organs and skeletal muscle is apparent.A subset of prion diseases, such as natural sheep scrapie, bovine spongiform encephalopathy, chronic wasting disease in deer and elk, and variant Creutzfeldt-Jakob disease in humans, are thought to be initiated by peripheral exposure to prions. Long before prions are found in the central nervous system, it is possible to detect prions in non-neuronal sites such as the lymphoreticular system or the muscular compartment. The events underlying the accumulation of prions within the muscular compartment remain enigmatic to date. In this proposal we aim to identify factors which contribute to prion accumulation within this compartment, focussing on the contribution of various cell types present in this niche such as peripheral nerves, lymphohaematopoetic cells and myoctyes.