Studies on peptide fragments of prion proteins

Publisher Summary The prion diseases are neurodegenerative disorders of humans and animals that are sporadic or inherited in origin and can be transmitted. Despite remarkable differences in phenotypic expression, these disorders share a similar pathogenic mechanism— that is, a post-translational modification of the prion protein from a normal cellular isoform (PrPC) to disease-specific species (PrPSc). Nuclear magnetic resonance (NMR) studies of recombinant murine, hamster, bovine, and human PrP indicate that the normal protein is composed of two structurally distinct moieties: an extended N-terminal segment with features of a flexibly disordered polypeptide chain, and a well-defined globular domain with three α helices and two-stranded antiparallel β sheet. The need to develop therapies for prion diseases has remarkably increased following the emergence of the new variant CJD. Although several compounds have been found to antagonize prion propagation in vitro or in vivo, the most suitable target for pharmacological therapy has not yet been identified.