The cellular prion protein (PrP) is essential to the long-term maintenance of myelin sheaths in peripheral nerves. PrP activates adhesion G-protein coupled receptor Adgrg6 on Schwann cells and initiates a pro-myelination cascade molecular signals. Because crucial for development regeneration after nerve injury, we investigated role repair. We performed experimental sciatic crush injuries co-iso...

The principal event underlying the development of prion disease is the conversion of soluble cellular prion protein (PrP(C)) into its disease-causing isoform, PrP(Sc). This conversion is associated with a marked change in secondary structure from predominantly α-helical to a high β-sheet content, ultimately leading to the formation of aggregates consisting of ordered fibrillar assemblies referr...

Prion diseases (e.g. ‘mad cow’ disease in cattle, chronic wasting disease in deer and elk, Creutzfeldt-Jakob disease in humans) have been a major public health concern affecting humans and almost all animals. However, dogs are strongly resistant to prion diseases. Recently, through transgenic techniques, it was reported that the single (surface) residue D159 is sufficient to confer protection a...

Prion diseases are fatal neurodegenerative conditions in humans and animals. In this review, we summarize the molecular background of phenotypic variability, relation of prion protein (PrP) to other proteins associated with neurodegenerative diseases, and pathogenesis of neuronal vulnerability. PrP exists in different forms that may be present in both diseased and non-diseased brain, however, a...

Yeast prions are heritable amyloid aggregates of functional yeast proteins; their propagation to subsequent cell generations is dependent upon fragmentation of prion protein aggregates by molecular chaperone proteins. Mounting evidence indicates the J-protein Sis1 may act as an amyloid specificity factor, recognizing prion and other amyloid aggregates and enabling Ssa and Hsp104 to act in prion...

Only a few years ago, pharmacotherapy of Creutzfeldt-Jakob disease was inconceivable. The enigmatic prion agent causing Creutzfeldt-Jakob disease, consisting solely of a misfolded conformational isoform, the scrapie prion protein, of the normal cellular prion protein was considered hard to treat by routine drug development. However, huge progress has been achieved in recent years, demonstrating...

Prions are infectious, self-propagating protein aggregates that have been identified in evolutionarily divergent members of the eukaryotic domain of life. Nevertheless, it is not yet known whether prokaryotes can support the formation of prion aggregates. Here we demonstrate that the yeast prion protein Sup35 can access an infectious conformation in Escherichia coli cells and that formation of ...

Within the CNS, the normal form of cellular prion protein (PrP(C)) is expressed on neurons, oligodendrocytes, and astrocytes. The contribution of these cell types to prion replication and pathogenesis is unclear. To assess the role of oligodendrocytes, we expressed PrP(C) under the control of the myelin basic protein (MBP) promoter in mice lacking endogenous PrP(C). PrP(C) was detected in oligo...

The central event in prion diseases is the conformational conversion of the cellular prion protein (PrP(C)) into PrP(Sc), a partially protease-resistant and infectious conformer. However, the mechanism by which PrP(Sc) causes neuronal dysfunction remains poorly understood. Levels of Shadoo (Sho), a protein that resembles the flexibly disordered N-terminal domain of PrP(C), were found to be redu...