Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders of humans and animals associated with an accumulation of abnormal isoforms of prion protein (PrP) in nerve cells. The pathogenesis of TSEs involves conformational conversions of normal cellular PrP (PrPc) to abnormal isoforms of PrP (PrPSc). While the protein-only hypothesis has been widely accepted as a causal mechanism of prion diseases, evidence from more recent research suggests a possible involvement of other cellular component(s) or as yet undefined infectious agent(s) in PrP pathogenesis. Although the underlying mechanisms of PrP strain variation and the determinants of interspecies transmissibility have not been fully elucidated, biochemical and molecular findings indicate that bovine spongiform encephalopathy in cattle and new-variant Creutzfeldt–Jakob disease in humans are caused by indistinguishable etiological agent(s). Cumulative evidence suggests that there may be risks of humans acquiring TSEs via a variety of exposures to infected material. The development of highly precise ligands is warranted to detect and differentiate strains, allelic variants and infectious isoforms of these PrPs. This article describes the general features of TSEs and PrP, the current understanding of their pathogenesis, recent advances in prion disease diagnostics, and PrP inactivation.

The transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative diseases that are also transmissible. The PrP protein is central to the disease process and has been hypothesised to be the infectious agent. Polymorphisms in the PrP gene have been linked to the incubation time of TSE disease, and mutations in the human PrP gene have been suggested to result in genetic TSE disease. Several PrP transgenic models have been developed. These models express PrP from different species, with and without PrP mutations, and at different levels of gene expression. This article discusses the contribution of these transgenic models to our present understanding of the TSE diseases.