Prion diseases (or transmissible spongiform encephalopathies) are a unique group of fatal progressive neurodegenerative diseases of the central nervous system. The infectious agent is hypothesized to consist solely of a highly protease-resistant misfolded isoform of the host prion protein. Prions display a remarkable degree of resistance to chemical and physical decontamination. Many common for...

Human prion diseases are fatal neurodegenerative disorders caused by misfolding of the prion protein. There are no useful biomarkers of disease progression. Cerebral cortex spongiform change, one of the classical pathological features of prion disease, resolves in prion-infected transgenic mice following prion protein gene knockout. We investigated the cross-sectional, longitudinal and post-mor...

Prion diseases, also known as Transmissible Spongiform Encephalopathies (TSEs), are fatal neurodegenerative disorders with characteristic sponge-like microscopic appearance in the infected brain. They are caused by a protein-only particle consisting of an abnormal isoform (PrPSc) of the normal ubiquitous cellular prion protein PrPc. Prion diseases affect both human and animals, and can cause in...

Human prion diseases are characterized by the conversion of the normal prion protein (PrP(C)) into a pathogenic isomer (PrP(Sc)). Distinct PrP(Sc) conformers are associated with different subtypes of prion diseases. PrP(C) binds copper and has antioxidation activity. Changes in metal-ion occupancy can lead to significant decline of the antioxidation activity and changes in conformation of the p...

The nascent polypeptide-associated complex (NAC) is a highly conserved but poorly characterized triad of proteins that bind near the ribosome exit tunnel. The NAC is the first cotranslational factor to bind to polypeptides and assist with their proper folding. Surprisingly, we found that deletion of NAC subunits in Saccharomyces cerevisiae rescues toxicity associated with the strong [PSI+] prio...

BACKGROUND No susceptibility genes have been identified in human prion disase, apart from the prion protein gene (PRNP). The gene SPRN, encodes Shadoo (Sho, shadow of prion protein) which has protein homology and possible functional links with the prion protein. METHODS A genetic screen was carried out of the open reading frame of SPRN by direct sequencing in 522 patients with prion disease, ...

Prions are kind of like Batman—they have a bad reputation, but they can also serve a number of good purposes. While prion domains—folded regions of proteins that can induce similar folding in other susceptible proteins—are responsible for the human prion diseases and may be involved in other neurodegenerative diseases as well, they have also been linked to normal processes of memory and innate ...

We investigated the conformational change in the human prion protein owing to an Ala→Val mutation by using molecular dynamics simulations. This mutation is related to Gerstmann-Sträussler-Sheinker disease, one of the familial prion diseases. Five prion protein structures were simulated in the periodic or non-periodic system. The results of molecular dynamics calculations indicated that the glob...