In the fungus Podospora anserina, the [Het-s] prion induces programmed cell death by activating the HET-S pore-forming protein. The HET-s β-solenoid prion fold serves as a template for converting the HET-S prion-forming domain into the same fold. This conversion, in turn, activates the HET-S pore-forming domain. The gene immediately adjacent to het-S encodes NWD2, a Nod-like receptor (NLR) with...

Yeast prions are non-Mendelian genetic elements that are conferred by altered and self-propagating protein conformations. Such a protein conformation-based transmission is similar to that of PrP(Sc), the infectious protein responsible for prion diseases. Despite recent progress in understanding the molecular nature and epigenetic transmission of prions, the underlying mechanisms governing prion...

While the conversion of the normal form of prion protein to a conformationally distinct pathogenic form is recognized to be the primary cause of prion disease, it is not clear how this leads to spongiform change, neuronal dysfunction and death. Mahogunin ring finger-1 (Mgrn1) and Attractin (Atrn) null mutant mice accumulate vacuoles throughout the brain that appear very similar to those associa...

TSEs (transmissible spongiform encephalopathies) are neurodegenerative diseases caused by pathogenic isoforms (PrPSc) of the host-encoded PrPc (cellular prion protein). After consumption of contaminated food, PrPSc deposits rapidly accumulate in lymphoid tissues before invasion of the CNS (central nervous system). However, the mechanisms of prion spreading from the periphery to the nervous syst...

The phenotypic and strain-related properties of human prion diseases are, according to the prion hypothesis, proposed to reside in the physicochemical properties of the conformationally altered, disease-associated isoform of the prion protein (PrP(Sc)), which accumulates in the brains of patients suffering from Creutzfeldt-Jakob disease and related conditions, such as Gerstmann-Straussler-Schei...

Prion diseases are associated with the conformational conversion of cellular prion protein (PrP(C)) to pathological β-sheet isoforms (PrP(Sc)), which is the infectious agent beyond comprehension. Increasing evidence indicated that an unknown toxic gain of function of PrP(sc) underlies neuronal death. Conversely, strong evidence indicated that cellular prion protein might be directly cytotoxic b...

found to be a minor component of amyloid plaques in Alzheimer's disease [19]. Alternatively, it is possible that there is an inhibitor of prion generation and propagation whose activity is inhibited by an excess of another prion. Excess Hsp104p cures [PSI + ] [20], excess Ydj1p (an Hsp40) can cure [URE3] [21], and Sis1p (another Hsp40) cures [RNQ + ] [22]. Overexpression of Ssb members of the H...

Misfolding of the cellular prion protein (PrPC) into the scrapie prion protein (PrPSc) results in progressive, fatal, transmissible neurodegenerative conditions termed prion diseases. Experimental and epidemiological evidence point toward a protracted, clinically silent phase in prion diseases, yet there is no diagnostic test capable of identifying asymptomatic individuals incubating prions. In...

The infectious cause of the transmissible spongiform encephalopathies (TSEs), or prion diseases, is not yet clearly defined. Although minorities of researchers cling tenaciously to the virus hypothesis, the prion or protein-only hypothesis is now widely accepted by most scientists working in this field (1). When originally formulated, the protein-only hypothesis proposed that the TSE agent was ...

Prion diseases in humans and animals comprise a group of invariably fatal neurodegenerative diseases characterized by the formation of a pathogenic protein conformer designated PrP(Sc) and infectious particles denoted prions. The cellular prion protein (PrP(C)) has a central role in the pathogenesis of prion disease. First, it is the precursor of PrP(Sc) and infectious prions and second, its ex...