Pathophysiology of prion accumulation in skeletal muscle

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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.