Pathophysiology of prion accumulation in skeletal muscle

先天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Pron蛋白的构象变化引起的。虽然Prion病只在中枢神经系统引起明显的形态损害，但明显累及非神经组织，如淋巴器官和骨骼肌。Pron病的一部分，如天然绵羊瘙痒病、牛海绵状脑病、鹿和麋鹿的慢性衰弱病，以及人类的变异型CreutzFeldt-Jakob病，被认为是由外周暴露于Prion引起的。早在中枢神经系统中发现普恩病毒之前，就有可能在非神经性部位检测到普恩病毒，如淋巴网状系统或肌肉间隔。到目前为止，在肌肉间隔内积累普鲁恩的基础事件仍然是个谜。在这项建议中，我们的目标是确定在这个隔室内导致Pron聚集的因素，重点放在这个利基中存在的各种细胞类型的贡献上，如周围神经、淋巴造血细胞和肌细胞。

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.