Mammalian prion diseases are fatal neurodegenerative disorders dependent on the prion protein PrP. Expansion of the oligopeptide repeats (ORE) found in PrP is associated with inherited prion diseases. Patients with ORE frequently harbor PrP aggregates, but other factors may contribute to pathology, as they often present with unexplained phenotypic variability. We created chimeric yeast-mammalia...

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 ...

Yeast and fungal prions are infectious proteins, most being self-propagating amyloids of normally soluble proteins. Their effects range from a very mild detriment to lethal, with specific effects dependent on the prion protein and the specific prion variant ("prion strain"). The prion amyloids of Sup35p, Ure2p, and Rnq1p are in-register, parallel, folded β-sheets, an architecture that naturally...

The role of Hsp70 chaperones in yeast prion propagation is well established. Highly conserved Hsp90 chaperones participate in a number of cellular processes, such as client protein maturation, protein degradation, cellular signalling and apoptosis, but little is known about their role in propagation of infectious prion like aggregates. Here, we examine the influence of Hsp90 in the maintenance ...

Prions are infectious proteins that are able to recruit a normal cellular prion protein and convert it into a prion. The mechanism of this conversion is unknown. Detailed analysis of the normal cellular prion protein and a corresponding prion has shown they possess identical post-translational modifications and differ solely in conformation. Recent work has suggested that the oxidized form of t...

A colleague and fellow immunologist, we will call her “Anne,” lifts her index and middle fingers on each hand and bows them in “air quotes” as she says prion “immunology” during my student’s thesis committee meeting. Anne says she works on “malaria, a real pathogen that elicits a real immune response.”Now, I am pretty sure Anne believes prions exist, but does she have a point about the immune r...

The human prion protein fragment, PrP (106-126), may contain a majority of the pathological features associated with the infectious scrapie isoform of PrP, known as PrP(Sc). Based on our previous findings that hypoxia protects neuronal cells from PrP (106-126)-induced apoptosis and increases cellular prion protein (PrP(C)) expression, we hypothesized that hypoxia-related genes, including hypoxi...

BACKGROUND Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder which affects widespread areas of the brainstem, basal ganglia and cerebral cortex. A number of proteins are known to accumulate in parkinsonian brains including ubiquitin and α-synuclein. Prion diseases are sporadic, genetic or infectious disorders with various clinical and histopathological features caused ...

This review examines recent attempts to advance the understanding of the mechanism by which neurones die in prion disease. Prion diseases or transmissible spongiform encephalopathies are characterized by the conversion of a normal glycoprotein, the prion protein, to a protease-resistant form that is suggested to be both the infectious agent and the cause of the rapid neurodegeneration in the di...