Cellular prion protein (PrP(C)) has the ability to trigger transmissible lethal diseases after in vivo maturation into a toxic amyloidogenic misfolded form (PrP(Sc)). Here, we use hydrogen exchange protection factors in restrained molecular dynamics simulations to characterize long-time scale fluctuations in human PrP(C). We find that the regions of residues 138-141 and 183-192 form new β-stran...

Transmissible mink encephalopathy (TME) is a rare disease of the North American mink, which has never been successfully transmitted to laboratory mice. We generated transgenic mice expressing the mink prion protein (PrP) and inoculated them with TME or the mouse-adapted scrapie strain 79A. TME infected mink PrP-transgenic mice on a murine PrP knockout background. The absolute species barrier be...

The central event underlying prion diseases involves conformational change of the cellular form of the prion protein (PrP(C)) into the disease-associated, transmissible form (PrP(Sc)). Pr(PC) is a sialoglycoprotein that contains two conserved N-glycosylation sites. Among the key parameters that control prion replication identified over the years are amino acid sequence of host PrP(C) and the st...

Prion diseases are caused by conformational alterations in the prion protein (PrP). The immune system has been assumed to be non-responsive to the self-prion protein, therefore, PrP autoimmunity has not been investigated. Here, we immunized various strains of mice with PrP peptides, some selected to fit the MHC class II-peptide binding motif. We found that specific PrP peptides elicited strong ...

The cellular prion protein (PrP(C)) is a glycosylphosphatidylinositol (GPI)-anchored protein present at the cell surface. PrP(C) N-terminal moiety is intrinsically disordered and is able to interact with a variety of ligands. Physiological ligands have neurotrophic activity, whilst others, including protein toxic oligomers, have neurotoxic functions. These two opposite activities involve differ...

Tg(PrP-EGFP) mice express an enhanced green fluorescent protein (EGFP)-tagged version of the prion protein (PrP) that behaves like endogenous PrP in terms of its posttranslational processing, anatomical localization, and functional activity. In this study, we describe experiments in which Tg(PrP-EGFP) mice were inoculated intracerebrally with scrapie prions. Although PrP-EGFP was incapable of s...

Natural sheep scrapie is a prion disease characterized by the accumulation of PrP(Sc) in brain and lymphoid tissues. Previous studies suggested that lymph node macrophages and follicular dendritic cells (FDC) accumulate PrP(Sc). In this study, lymph nodes were analyzed for the presence of PrP(Sc) and macrophage or FDC markers using dual immunohistochemistry. A monoclonal antibody (mAb) to the C...

The conformational conversion of the cellular prion protein, PrP(C), to the misfolded isoform PrP(Sc )is the central pathogenic event in the uniquely transmissible neurodegenerative prion diseases. As both PrP(C) and PrP(Sc) are associated with membranes, the nature of the membrane microenvironment may well play a significant role in both the conformational conversion process as well as the nor...

Prion diseases are fatal neurodegenerative disorders with unique transmissible properties. The infectious and pathological agent is thought to be a misfolded conformer of the prion protein. Little is known about the initial events in prion infection because the infecting prion source has been immunologically indistinguishable from normal cellular prion protein (PrP(C)). Here we develop a unique...