Beyond PrP9res) type 1/type 2 dichotomy in Creutzfeldt-Jakob disease

Autor: Uro-Coste, Emmanuelle, Cassard, Hervé, Simon, Stéphanie, Lugan, Séverine, Bilheude, Jean-Marc, Perret-Liaudet, Armand, Ironside, James, Haik, Stéphane, Basset-Leobon, Christelle, Lacroux, Caroline, Peoch', Katell, Streichenberger, Nathalie, Langeveld, Jan, Head, Mark, Grassi, Jacques, Hauw, Jean-Jacques, Schelcher, Francois, Delisle, Marie Bernadette, Andréoletti, Olivier
Přispěvatelé: Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), Service de Pharmacologie et d'Immunologie (DRM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Bio-Rad, Research and Development Department, BIO-RAD, Services de Neurochimie et de Pathologie, Hôpital Neurologique de Bron, National Creutzfeldt-Jakob Disease Surveillance Unit, Division of Pathology, University of Edinburgh-Western General Hospital, Maladies à Prions chez l'Homme, Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Neuropathologie Raymond Escourolle [CHU Pitié-Salpétriêre], Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Biochimie et Biologie Moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Central Institute for Animal Disease Control CIDC-Lelystad, Central Institute for Animal Disease Control, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de Neuropathologie Raymond Escourolle, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière, Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC)
Jazyk: angličtina
Rok vydání: 2008
Předmět:
lcsh:Immunologic diseases. Allergy
PrPSc Proteins
Protein Conformation
animal diseases
Blotting
Western
Enzyme-Linked Immunosorbent Assay
MESH: Protein Isoforms
Creutzfeldt-Jakob Syndrome
MESH: Brain
MESH: Protein Conformation
Species Specificity
Humans
Protein Isoforms
MESH: Blotting
Western
MESH: Species Specificity
MESH: Brain Chemistry
MESH: Genetic Variation
lcsh:QH301-705.5
[SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases
Brain Chemistry
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases
MESH: Humans
Blotting
MESH: PrPSc Proteins
Genetic Variation
Brain
MESH: Enzyme-Linked Immunosorbent Assay
MESH: Creutzfeldt-Jakob Syndrome
nervous system diseases
Neurological Disorders/Prion Diseases
lcsh:Biology (General)
lcsh:RC581-607
Western
Research Article
Zdroj: PLoS Pathogens
PLoS Pathogens, 2008, 4 (3), pp.e1000029. ⟨10.1371/journal.ppat.1000029⟩
PLoS Pathogens, Public Library of Science, 2008, 4 (3), pp.e1000029. ⟨10.1371/journal.ppat.1000029⟩
PLoS Pathogens, Vol 4, Iss 3, p e1000029 (2008)
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1000029⟩
Popis: Sporadic Creutzfeldt-Jakob disease (sCJD) cases are currently subclassified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the proteinase K (PK) digested abnormal prion protein (PrPres) identified on Western blotting (type 1 or type 2). These biochemically distinct PrPres types have been considered to represent potential distinct prion strains. However, since cases of CJD show co-occurrence of type 1 and type 2 PrPres in the brain, the basis of this classification system and its relationship to agent strain are under discussion. Different brain areas from 41 sCJD and 12 iatrogenic CJD (iCJD) cases were investigated, using Western blotting for PrPres and two other biochemical assays reflecting the behaviour of the disease-associated form of the prion protein (PrPSc) under variable PK digestion conditions. In 30% of cases, both type 1 and type 2 PrPres were identified. Despite this, the other two biochemical assays found that PrPSc from an individual patient demonstrated uniform biochemical properties. Moreover, in sCJD, four distinct biochemical PrPSc subgroups were identified that correlated with the current sCJD clinico-pathological classification. In iCJD, four similar biochemical clusters were observed, but these did not correlate to any particular PRNP 129 polymorphism or western blot PrPres pattern. The identification of four different PrPSc biochemical subgroups in sCJD and iCJD, irrespective of the PRNP polymorphism at codon 129 and the PrPres isoform provides an alternative biochemical definition of PrPSc diversity and new insight in the perception of Human TSE agents variability.
Author Summary Prion diseases are transmissible neurodegenerative disorders characterized by accumulation of an abnormal isoform (PrPSc) of a host-encoded protein (PrPC) in affected tissues. According to the prion hypothesis, PrPSc alone constitutes the infectious agent. Sporadic Creutzfeldt-Jakob disease (sCJD) is the commonest human prion disease. Although considered as a spontaneous disorder, the clinicopathological phenotype of sCJD is variable and substantially influenced by the methionine/valine polymorphism at codon 129 of the prion protein gene (PRNP). Based on these clinicopathological and genetic criteria, a subclassification of sCJD has been proposed. Here, we used two new biochemical assays that identified four distinct biochemical PrPSc subgroups in a cohort of 41 sCJD cases. These subgroups correlate with the current sCJD subclassification and could therefore represent distinct prion strains. Iatrogenic CJD (iCJD) occurs following presumed accidental human-to-human sCJD transmission. Our biochemical investigations on 12 iCJD cases from different countries found the same four subgroups as in sCJD. However, in contrast to the sCJD cases, no particular correlation between the PRNP codon 129 polymorphism and biochemical PrPSc phenotype could be established in iCJD cases. This study provides an alternative biochemical definition of PrPSc diversity in human prion diseases and new insights into the perception of agent variability.
Databáze: OpenAIRE
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