The prion was defined by Stanley Prusiner as the infectious agent that causes transmissible spongiform encephalopathies and equated with the prion protein PrPSc. Its cognate gene, Prnp, was identified by Charles Weissmann in Zurich, and shown to encode the host protein PrPC. Since the latter discovery, transgenic mice have contributed many important insights to the field of prion biology, inclu...

Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy (TSE) of cattle and was first detected in 1986 in the United Kingdom. It is the most likely cause of variant Creutzfeldt-Jakob disease (CJD) in humans. The origin of BSE remains an enigma. Here we report an H-type BSE case associated with the novel mutation E211K within the prion protein gene (Prnp). Sequence an...

Prion diseases such as scrapie in sheep, bovine spongiform encephalopathy in cattle, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease and fatal familial insomnia in man are neurodegenerative disorders. In humans, the diseases can be sporadic, inherited, or acquired by infection. The underlying pathogenic event in prion diseases is a conformational modification of the cellular i...

Background: Scrapie is the transmissible spongiform encephalopathy in sheep. Because genetic variants of the ovine PrP gene (PRNP) can be associated with disease risk, the European Union initiated programs to eradicate high-risk PRNP genotypes from sheep livestock. For this purpose, reliable and cost-effective genotyping is needed. Methods: We amplified DNA to cover the 3 risk codons in exon 3 ...

UNLABELLED Interaction of prion protein and amyloid-b oligomers has been demonstrated recently. Homozygosity at prion protein gene (PRNP) codon 129 is associated with higher risk for Creutzfeldt-Jakob disease. This polymorphism has been addressed as a possible risk factor in Alzheimer disease (AD). OBJECTIVE To describe the association between codon 129 polymorphisms and AD. METHODS We inve...

Inherited prion diseases are neurodegenerative disorders caused by autosomal dominant mutations in the human prion protein gene (PRNP). Kindred with inherited prion disease can show remarkable phenotypic variability that has yet to be explained. Here we report analysis of protease resistant disease-related prion protein (PrP(Sc)) isoforms from a range of inherited prion disease cases (point mut...

The prion protein (PrP) is highly conserved and ubiquitously expressed, suggesting that it plays an important physiological function. However, despite decades of investigation, this role remains elusive. Here, by using animal and cellular models, we unveil a key role of PrP in the DNA damage response. Exposure of neurons to a genotoxic stress activates PRNP transcription leading to an increased...

Structural alterations of the cellular prion protein (PrP(C)) seem to be the core of the pathogenesis of prion diseases. However, the physiological function of PrP(C )remains an enigma. Cell culture experiments have indicated that PrP(C) and in particular its N-terminal octarepeat region together with the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways have a fundamental involvement...

BACKGROUND In 2006, an atypical U.S. case of bovine spongiform encephalopathy (BSE) was discovered in Alabama and later reported to be polymorphic for glutamate (E) and lysine (K) codons at position 211 in the bovine prion protein gene (Prnp) coding sequence. A bovine E211K mutation is important because it is analogous to the most common pathogenic mutation in humans (E200K) which causes heredi...

OBJECTIVE To perform prion protein gene (PRNP) codon 129 analysis in DNA extracted from appendix tissue samples that had tested positive for disease associated prion protein. DESIGN Reanalysis of positive cases identified in a retrospective anonymised unlinked prevalence study of variant Creutzfeldt-Jakob disease (vCJD) in the United Kingdom. STUDY SAMPLES Three positive appendix tissue sam...