The state of the prion

MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Nature Reviews Microbiology (Impact Factor: 23.57). 12/2004; 2(11):861-71. DOI: 10.1038/nrmicro1025
Source: PubMed


There is little doubt that the main component of the transmissible agent of spongiform encephalopathies - the prion - is a conformational variant of the ubiquitous host protein PrP(C), and that the differing properties of various prion strains are associated with different abnormal conformations of this protein. The precise structure of the prion is not yet known, nor are the mechanisms of infection, conformational conversion and pathogenesis understood.

Download full-text


Available from: Charles Weissmann, Mar 31, 2015
29 Reads
  • Source
    • "Therefore, elevated expression level of PRNP may increase the antioxidant defense in the torpid brain. Because PRNP has diverse vital roles in nervous system and tumorigenesis [58], [59], we hypothesized that up-regulation of PRNP is involved in the maintenance of neural morphology and anti-apoptosis during the torpor. Superoxide dismutase, an important antioxidant, eliminates free radicals in the body. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hibernation is an energy-saving strategy which is widely adopted by heterothermic mammals to survive in the harsh environment. The greater horseshoe bat (Rhinolophus ferrumequinum) can hibernate for a long period in the hibernation season. However, the global gene expression changes between hibernation and non-hibernation season in the greater horseshoe bat remain largely unknown. We herein reported a comprehensive survey of differential gene expression in the brain between winter hibernating and summer active greater horseshoe bats using next-generation sequencing technology. A total of 90,314,174 reads were generated and we identified 1,573 differentially expressed genes between active and torpid states. Interestingly, we found that differentially expressed genes are over-represented in some GO categories (such as metabolic suppression, cellular stress responses and oxidative stress), which suggests neuroprotective strategies might play an important role in hibernation control mechanisms. Our results determined to what extent the brain tissue of the greater horseshoe bats differ in gene expression between summer active and winter hibernating states and provided comprehensive insights into the adaptive mechanisms of bat hibernation.
    PLoS ONE 09/2014; 9(9):e107746. DOI:10.1371/journal.pone.0107746 · 3.23 Impact Factor
  • Source
    • "Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative disorders that include Creutzfeldt-Jakob disease in humans, scrapie in sheep, chronic wasting disease in cervids, and bovine spongiform encephalopathy in cattle (Aguzzi and Polymenidou, 2004; Caughey et al., 2009; Cobb and Surewicz, 2009; Collinge, 2001; Prusiner, 1998; Weissmann, 2004). The prion hypothesis asserts that the transmission of TSEs does not require nucleic acids, and that the infectious TSE agent is proteinaceous in nature, consisting of a misfolded form of prion protein (PrP) (Prusiner, 1982). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Prion diseases, or transmissible spongiform encephalopathies (TSEs), are associated with the conformational conversion of the cellular prion protein, PrP(C), into a protease-resistant form, PrP(Sc). Here, we show that mutation-induced thermodynamic stabilization of the folded, α-helical domain of PrP(C) has a dramatic inhibitory effect on the conformational conversion of prion protein in vitro, as well as on the propagation of TSE disease in vivo. Transgenic mice expressing a human prion protein variant with increased thermodynamic stability were found to be much more resistant to infection with the TSE agent than those expressing wild-type human prion protein, in both the primary passage and three subsequent subpassages. These findings not only provide a line of evidence in support of the protein-only model of TSEs but also yield insight into the molecular nature of the PrP(C)→PrP(Sc) conformational transition, and they suggest an approach to the treatment of prion diseases.
    Cell Reports 07/2013; 4(2). DOI:10.1016/j.celrep.2013.06.030 · 8.36 Impact Factor
  • Source
    • "More recently, studies on enzymatic degradation of prion protein have highlighted the ability of some proteases to digest this class of protein [7-9]. Prion diseases are fatal neurodegenerative disorders that include Creutzfeldt-Jacob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia, and kuru in humans, bovine spongiform encephalopathy (BSE) in cattle, and scrapie in sheep [10,11]. Their central feature is the posttranslational conversion of host-encoded, cellular prion protein (PrPC) to an abnormal isoform, known as PrPSc. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Tk-SP is a member of subtilisin-like serine proteases from a hyperthermophilic archaeon Thermococcus kodakarensis. It has been known that the hyper-stable protease, Tk-SP, could exhibit enzymatic activity even at high temperature and in the presence of chemical denaturants. In this work, the enzymatic activity of Tk-SP was measured in the presence of detergents and EDTA. In addition, we focused to demonstrate that Tk-SP could degrade the abnormal prion protein (PrPSc), a protease-resistant isoform of normal prion protein (PrPC). Results Tk-SP was observed to maintain its proteolytic activity with nonionic surfactants and EDTA at 80°C. We optimized the condition in which Tk-SP functions efficiently, and demonstrated that the enzyme is highly stable in the presence of 0.05% (w/v) nonionic surfactants and 0.01% (w/v) EDTA, retaining up to 80% of its activity. Additionally, we also found that Tk-SP can degrade PrPSc to a level undetectable by western-blot analysis. Conclusions Our results indicate that Tk-SP has a great potential for technological applications, such as thermo-stable detergent additives. In addition, it is also suggested that Tk-SP-containing detergents can be developed to decrease the secondary infection risks of transmissible spongiform encephalopathies (TSE).
    BMC Biotechnology 02/2013; 13(1):19. DOI:10.1186/1472-6750-13-19 · 2.03 Impact Factor
Show more