Biochemical and strain properties of CJD prions: complexity versus simplicity

Authors

  • Stéphane Haïk,

    1. Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l’Institut du Cerveau et de la Moelle épinière (CRICM), UMRS 975, Equipe “Alzheimer’s and Prion diseases”, Paris, France
    2. Inserm, U 975, Paris, France
    3. CNRS, UMR 7225, Paris, France
    4. AP-HP, Groupe hospitalier Pitié-Salpêtrière, Cellule Nationale de Référence des Maladies de Creutzfeldt-Jakob, Paris, France
    5. Centre National de Référence des Agents Transmissibles Non Conventionnels, Paris, France
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  • Jean-Philippe Brandel

    1. Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l’Institut du Cerveau et de la Moelle épinière (CRICM), UMRS 975, Equipe “Alzheimer’s and Prion diseases”, Paris, France
    2. Inserm, U 975, Paris, France
    3. CNRS, UMR 7225, Paris, France
    4. AP-HP, Groupe hospitalier Pitié-Salpêtrière, Cellule Nationale de Référence des Maladies de Creutzfeldt-Jakob, Paris, France
    5. Centre National de Référence des Agents Transmissibles Non Conventionnels, Paris, France
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Address correspondence and reprint requests to Stéphane Haïk, ICM, Hôpital Pitié-Salpêtrière, 47 boulevard de l’Hôpital, 75 013 Paris, France. E-mail: stephane.haik@upmc.fr

Abstract

J. Neurochem. (2011) 119, 251–261.

Abstract

Prions, the agents responsible for transmissible spongiform encephalopathies, are infectious proteins consisting primarily of scrapie prion protein (PrPSc), a misfolded, β-sheet enriched and aggregated form of the host-encoded cellular prion protein (PrPC). Their propagation is based on an autocatalytic PrP conversion process. Despite the lack of a nucleic acid genome, different prion strains have been isolated from animal diseases. Increasing evidence supports the view that strain-specific properties may be enciphered within conformational variations of PrPSc. In humans, sporadic Creutzfeldt-Jakob disease (sCJD) is the most frequent form of prion diseases and has demonstrated a wide phenotypic and molecular spectrum. In contrast, variant Creutzfeldt-Jakob disease (vCJD), which results from oral exposure to the agent of bovine spongiform encephalopathy, is a highly stereotyped disease, that, until now, has only occurred in patients who are methionine homozygous at codon 129 of the PrP gene. Recent research has provided consistent evidence of strain diversity in sCJD and also, unexpectedly enough, in vCJD. Here, we discuss the puzzling biochemical/pathological diversity of human prion disorders and the relationship of that diversity to the biological properties of the agent as demonstrated by strain typing in experimental models.

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