The transmissible spongiform encephalopathies

Abstract

Transmissible spongiform encephalopathies (TSEs) represent a group of neurodegenerative diseases characterised by a very long incubation period in regard to the life expectancy of the host species. The lesions are restricted to the central nervous system, although the pathogenesis of infection implies a primary replication step of TSE agents in the lymphoid organs followed by a neuroinvasive phase. The outcome is always fatal and today there is neither cure nor prophylaxis for these diseases. For years, the causative agents of TSEs have posed a conundrum in terms of current knowledge of microorganisms, and there are still open questions about their exact nature. They are usually called TSE agents or prions because they are thoughtto be primarily composed of a modified host protein, the prion protein (PrP). A pathological form of the prion protein, called PrPSc (for scrapie) or PrPRes, an operational definition referring to resistance to proteolytic digestion, accumulates in target organs. The aim of this introductory chapter is to presentthe general features of TSEs and a modern understanding of TSE agents and their mode of replication. Notwithstanding the plethora of unsolved questions on these diseases and their aetiology, knowledge of their pathogenesis and recent advances in understanding of the molecular basis of PrP accumulation, together with detection systems, provide the tools to conduct sound TSE risk management.