Transmissible Spongiform Encephalopathies

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Bruce Chesebro - One of the best experts on this subject based on the ideXlab platform.

  • introduction to the Transmissible Spongiform Encephalopathies or prion diseases
    British Medical Bulletin, 2003
    Co-Authors: Bruce Chesebro
    Abstract:

    Sheep scrapie has been known for at least 200 years and was described as a Transmissible disease over 100 years ago. Since then, three groups of Transmissible Spongiform Encephalopathies or TSE diseases have been identified in humans including familial, infectious and sporadic types. The discovery of the prion protein (PrP) in the 1980s greatly accelerated knowledge of the biology and pathogenesis of TSE diseases as this protein was found to play a critical role in disease susceptibility and the TSE species-barrier and may also be a component of the infectious agent itself. Nevertheless, the nature of the TSE agents remains an enigma. Proof of the protein-only hypothesis may require generation of biologically active Transmissible agent in a cell-free environment where a virus cannot replicate. Conversely, proof of a viral aetiology will require identification and isolation of a candidate virus. Further understanding of the structure of the disease-associated protease-resistant PrP should help elucidate the mechanism of PrP conversion from the normal to the abnormal form. Such information should open up new approaches to both diagnosis and therapy.

  • Transmissible Spongiform Encephalopathies and prion protein interconversions
    Advances in Virus Research, 2001
    Co-Authors: Byron Caughey, Bruce Chesebro
    Abstract:

    Publisher Summary This chapter discusses important natural human and animal Transmissible Spongiform Encephalopathies (TSE) diseases and various experimental models. It also summarizes prion protein (PrP) biochemistry and cell biology, especially as it relates to the TSE-associated conversion of PrPc to PrP-res. TSE diseases, or prion diseases, are rare, fatal neurodegenerative diseases of humans and other animals. They are Transmissible by inoculation or ingestion of infected tissues. Their primary symptoms in humans are dementia and ataxia. These diseases are usually characterized by Spongiform degeneration of the brain, accompanied by the appearance of activated astrocytes. Most distinctive, however, is the accumulation of abnormal protease-resistant forms of host-derived PrP in the central nervous system and, to a lesser extent, in lymphoreticular tissues. Much evidence suggests that abnormal forms of PrP of some sort are critical in the transmission and pathogenesis of TSE diseases. TSE diseases in humans can be divided into three groups—namely, sporadic, familial, and iatrogenic. Familial TSE diseases are all associated with different mutations in the PrP gene and include familial Creutzfeldt–Jakob disease, Gerstmann–Straussler–Scheinker syndrome, and fatal familial insomnia.

  • Prion protein and the Transmissible Spongiform Encephalopathies.
    Trends in cell biology, 1997
    Co-Authors: Byron Caughey, Bruce Chesebro
    Abstract:

    Transmissible Spongiform Encephalopathies (TSEs) are fatal neurodegenerative diseases that occur in a wide variety of mammals. In humans, TSE diseases include kuru, sporadic and iatrogenic Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI). So far, TSE diseases occur only rarely in humans; however, scrapie is a widespread problem in sheep, and the recent epidemic of bovine Spongiform encephalopathy (BSE or mad cow disease) has seriously affected the British cattle industry. Of special concern is the recent appearance of a new variant of CJD in humans that is suspected of being caused by infections from BSE-infected cattle products. In all these diseases, an abnormal form of a host protein, prion protein (PrP), is essential for the pathogenic process. The relationship of this protein to the Transmissible agent is currently the subject of great interest and controversy and is the subject of this review.

Byron Caughey - One of the best experts on this subject based on the ideXlab platform.

  • Cell death and autophagy in prion diseases (Transmissible Spongiform Encephalopathies)
    Folia neuropathologica, 2008
    Co-Authors: Pawel P. Liberski, Byron Caughey, David R. Brown, Beata Sikorska, Paul Brown
    Abstract:

    Neuronal autophagy, like apoptosis, is one of the mechanisms of programmed cell death. In this review, we summarize current information about autophagy in naturally occurring and experimentally induced scrapie, Creutzfeldt-Jakob disease and Gerstmann-Straussler-Scheinker syndrome against the broad background of neural degenerations in Transmissible Spongiform Encephalopathies (TSEs). Typically a sequence of events is observed: from a part of the neuronal cytoplasm sequestrated by concentric arrays of double membranes (phagophores); through the enclosure of the cytoplasm and membrane proliferation; to a final transformation of the large area of the cytoplasm into a collection of autophagic vacuoles of different sizes. These autophagic vacuoles form not only in neuronal perikarya but also in neurites and synapses. On the basis of ultrastructural studies, we suggest that autophagy may play a major role in Transmissible Spongiform Encephalopathies and may even participate in the formation of Spongiform change.

  • Transmissible Spongiform Encephalopathies and prion protein interconversions
    Advances in Virus Research, 2001
    Co-Authors: Byron Caughey, Bruce Chesebro
    Abstract:

    Publisher Summary This chapter discusses important natural human and animal Transmissible Spongiform Encephalopathies (TSE) diseases and various experimental models. It also summarizes prion protein (PrP) biochemistry and cell biology, especially as it relates to the TSE-associated conversion of PrPc to PrP-res. TSE diseases, or prion diseases, are rare, fatal neurodegenerative diseases of humans and other animals. They are Transmissible by inoculation or ingestion of infected tissues. Their primary symptoms in humans are dementia and ataxia. These diseases are usually characterized by Spongiform degeneration of the brain, accompanied by the appearance of activated astrocytes. Most distinctive, however, is the accumulation of abnormal protease-resistant forms of host-derived PrP in the central nervous system and, to a lesser extent, in lymphoreticular tissues. Much evidence suggests that abnormal forms of PrP of some sort are critical in the transmission and pathogenesis of TSE diseases. TSE diseases in humans can be divided into three groups—namely, sporadic, familial, and iatrogenic. Familial TSE diseases are all associated with different mutations in the PrP gene and include familial Creutzfeldt–Jakob disease, Gerstmann–Straussler–Scheinker syndrome, and fatal familial insomnia.

  • Prion protein interconversions and the Transmissible Spongiform Encephalopathies
    Structure (London England : 1993), 1999
    Co-Authors: Motohiro Horiuchi, Byron Caughey
    Abstract:

    Autocatalytic changes in the conformation and aggregation state of prion protein appear to be fundamental to Transmissible Spongiform Encephalopathies or prion diseases. Here we review the considerable progress that has been made in describing the normal properties of prion protein and the changes that occur during these devastating neurodegenerative diseases.

  • Prion protein and the Transmissible Spongiform Encephalopathies.
    Trends in cell biology, 1997
    Co-Authors: Byron Caughey, Bruce Chesebro
    Abstract:

    Transmissible Spongiform Encephalopathies (TSEs) are fatal neurodegenerative diseases that occur in a wide variety of mammals. In humans, TSE diseases include kuru, sporadic and iatrogenic Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI). So far, TSE diseases occur only rarely in humans; however, scrapie is a widespread problem in sheep, and the recent epidemic of bovine Spongiform encephalopathy (BSE or mad cow disease) has seriously affected the British cattle industry. Of special concern is the recent appearance of a new variant of CJD in humans that is suspected of being caused by infections from BSE-infected cattle products. In all these diseases, an abnormal form of a host protein, prion protein (PrP), is essential for the pathogenic process. The relationship of this protein to the Transmissible agent is currently the subject of great interest and controversy and is the subject of this review.

Sylvain Lehmann - One of the best experts on this subject based on the ideXlab platform.

  • Oxidative stress and the prion protein in Transmissible Spongiform Encephalopathies.
    Brain research. Brain research reviews, 2002
    Co-Authors: Ollivier Milhavet, Sylvain Lehmann
    Abstract:

    Transmissible Spongiform Encephalopathies form a group of fatal neurodegenerative disorders that have the unique property of being infectious, sporadic or genetic in origin. These diseases are believed to be the consequence of the conformational conversion of the prion protein into an abnormal isoform. Their exact pathogenic mechanism remains uncertain, but it is believed that oxidative stress plays a central role. In this article, we will first review in detail the data supporting the latter hypothesis. Subsequently, we will discuss the relationship between the prion protein and the cellular response to oxidative stress, attempting ultimately to link PrP function and neurodegeneration in these disorders.

  • effect of amphotericin b on wild type and mutated prion proteins in cultured cells putative mechanism of action in Transmissible Spongiform Encephalopathies
    Journal of Neurochemistry, 2001
    Co-Authors: Alain Mangé, Ollivier Milhavet, Hilary E M Mcmahon, Danielle Casanova, Sylvain Lehmann
    Abstract:

    Abstract: Transmissible Spongiform Encephalopathies form a group of fatal neurodegenerative disorders that have the unique property of being infectious, sporadic, or genetic in origin. Although some doubts remain on the nature of the responsible agent of these diseases, it is clear that a protein called PrPSc [the scrapie isoform of prion protein (PrP)] plays a central role. PrPSc represents a conformational variant of PrPC (the cellular isoform of PrP), the normal host protein. Polyene antibiotics, such as amphotericin B, have been shown to delay the accumulation of PrPSc and to increase the incubation time of the disease after experimental transmission in laboratory animals. Unlike agents such as Congo red, the inhibitory effect of amphotericin B on PrPSc generation has not been observed in infected cultures. Using transfected cells expressing wild-type or mutated mouse PrPs, we show here that amphotericin B is able to interfere with the generation of abnormal PrP isoforms in culture. Its action seems related to a modification of PrP trafficking through the association of this glycosylphosphatidylinositol-anchored protein with detergent-resistant microdomains. These results represent a first step toward the comprehension of the mechanism of action of amphotericin B in Transmissible Spongiform Encephalopathies.

  • Cell culture models of Transmissible Spongiform Encephalopathies.
    Biochemical and biophysical research communications, 2001
    Co-Authors: Florence Béranger, Alain Mangé, Jérôme Solassol, Sylvain Lehmann
    Abstract:

    In this review, we describe the generation and use of cell culture models of Transmissible Spongiform Encephalopathies, also known as prion diseases. These models include chronically prion-infected cell lines, as well as cultures expressing variable amounts of wild-type, mutated, or chimeric prion proteins. These cell lines have been widely used to investigate the biology of both the normal and the pathological isoform of the prion protein. They have also contributed to the comprehension of the pathogenic processes occurring in Transmissible Spongiform Encephalopathies and in the development of new therapeutic approaches of these diseases.

Claudio Soto - One of the best experts on this subject based on the ideXlab platform.

  • role of prion protein oligomers in the pathogenesis of Transmissible Spongiform Encephalopathies
    2012
    Co-Authors: Claudio Soto, Rodrigo Morales, Claudia Durananiotz
    Abstract:

    Prion diseases, also known as Transmissible Spongiform ­Encephalopathies, are a group of neurodegenerative disorders associated with misfolding and aggregation of prion proteins. Although it is not completely known how structural changes in the prion protein induce neurodegeneration, it is widely accepted that formation of the misfolded prion protein (termed PrPSc) is both the triggering event in the ­disease and the main component of the infectious agent responsible for disease transmission. A long-debated issue in prion diseases has been the exact composition and size of the PrPSc particle required for initiating brain degeneration and propagating disease. Old and recent evidence show that PrPSc is an oligomer composed of ­several units of the prion protein monomer, folded into a β-sheet-rich conformation. In this article we discuss the potential roles of prion oligomers in both neurotoxicity and infectivity and the similarities of prion diseases to other neurodegenerative ­diseases associated with protein misfolding and aggregation.

  • Altering prion replication for therapy and diagnosis of Transmissible Spongiform Encephalopathies.
    Biochemical Society transactions, 2002
    Co-Authors: Claudio Soto
    Abstract:

    Transmissible Spongiform Encephalopathies, also known as prion-related diseases, are a group of fatal neurodegenerative disorders associated with the misfolding of the prion protein. In this article, the potential use of the principles of prion replication to develop novel therapeutic and diagnostic strategies for these devastating diseases are described.

Jesús De Pedro-cuesta - One of the best experts on this subject based on the ideXlab platform.

  • Human Transmissible Spongiform Encephalopathies in eleven countries: diagnostic pattern across time, 1993-2002.
    BMC public health, 2006
    Co-Authors: Jesús De Pedro-cuesta, Maurizio Pocchiari, Markus Glatzel, Javier Almazán, Katharina Stoeck, Vittorio Mellina, Maria Puopolo, Inga Zerr, Hans A Kretszchmar, Jean-philippe Brandel
    Abstract:

    Background The objective of this study was to describe the diagnostic panorama of human Transmissible Spongiform Encephalopathies across 11 countries.

  • Trends in scientific activity addressing Transmissible Spongiform Encephalopathies: a bibliometric study covering the period 1973-2002.
    BMC public health, 2006
    Co-Authors: Elías Sanz-casado, Margarita Ramírez-de Santa Pau, Carlos Suárez-balseiro, Isabel Iribarren-maestro, Jesús De Pedro-cuesta
    Abstract:

    Background The purpose of this study is to analyse the trends in scientific research on Transmissible Spongiform Encephalopathies by applying bibliometric tools to the scientific literature published between 1973 and 2002.

  • Human Transmissible Spongiform Encephalopathies in eleven countries: diagnostic pattern across time, 1993-2002.
    BMC Public Health, 2006
    Co-Authors: Jesús De Pedro-cuesta, Maurizio Pocchiari, Markus Glatzel, Javier Almazán, Katharina Stoeck, Vittorio Mellina, Maria Puopolo, Inga Zerr, Hans A Kretszchmar, Jean-philippe Brandel
    Abstract:

    BACKGROUND: The objective of this study was to describe the diagnostic panorama of human Transmissible Spongiform Encephalopathies across 11 countries. METHODS: From data collected for surveillance purposes, we describe annual proportions of deaths due to different human Transmissible Spongiform Encephalopathies in eleven EUROCJD-consortium countries over the period 1993-2002, as well as variations in the use of diagnostic tests. Using logistic models we quantified international differences and changes across time. RESULTS: In general, pre-mortem use of diagnostic investigations increased with time. International differences in pathological confirmation of sporadic Creutzfeldt-Jakob disease, stable over time, were evident. Compared to their counterparts, some countries displayed remarkable patterns, such as: 1) the high proportion, increasing with time, of variant Creutzfeldt-Jakob disease in the United Kingdom, (OR 607.99 95% CI 84.72-4363.40), and France (OR 18.35, 95% CI 2.20-152.83); 2) high, decreasing proportions of iatrogenic Creutzfeldt-Jakob disease in France, (OR 5.81 95% CI 4.09-8.24), and the United Kingdom, (OR 1.54 95% CI 1.03-2.30); and, 3) high and stable ratios of genetic forms in Slovakia (OR 21.82 95% CI 12.42-38.33) and Italy (OR 2.12 95% CI 1.69-2.68). CONCLUSION: Considerable international variation in aetiological subtypes of human Transmissible Spongiform Encephalopathies was evident over the observation period. With the exception of variant Creutzfeldt-Jakob disease and iatrogenic Creutzfeldt-Jakob disease in France and the United Kingdom, these differences persisted across time.