[Prion diseases or transmissible spongiform encephalopathies]

Abstract

Prion diseases or transmissible spongiform encephalopathies (TSEs) are human and animal diseases naturally or experimentally transmissible with a long incubation period and a fatal course without remission. The nature of the transmissible agent remains debated but the absence of a structure evoking a conventional microorganism led Stanley B. Prusiner to hypothesize that it could be an infectious protein (proteinaceous infectious particle or prion). The prion would be the abnormal form of a normal protein, cellular PrP (PrP^c) which will change its spatial conformation and be converted into scrapie prion protein (PrP^sc) with properties of partial resistance to proteases, aggregation and insolubility in detergents. No inflammatory or immune response are detected in TSEs which are characterized by brain damage combining spongiosis, neuronal loss, astrocytic gliosis, and deposits of PrP^sc that may appear as amyloid plaques. Although the link between the accumulation of PrP^sc and the appearance of lesions remains debated, the presence of PrP^sc is constant during TSE and necessary for a definitive diagnosis. Even if they remain rare diseases (2 cases per million), the identification of kuru, at the end of the 1950s, of iatrogenic cases in the course of the 1970s and of the variant of Creutzfeldt-Jakob disease (CJD) in the mid-1990s explain the interest in these diseases but also the fears they can raise for public health. They remain an exciting research model because they belong both to the group of neurodegenerative diseases with protein accumulation (sporadic CJD), to the group of communicable diseases (iatrogenic CJD, variant of CJD) but also to the group of genetic diseases with a transmission Mendelian dominant (genetic CJD, Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia).

Keywords: Creutzfeldt-Jakob disease; Encéphalopathie spongiforme transmissible; Fatal familial insomnia; Gerstmann-Straussler-Scheinker; Insomnie fatale familiale; Kuru; Maladie de Creutzfeldt-Jakob; Prion; Transmissible spongiform encephalopathies; Variant of Creutzfeldt-Jakob disease; Variante de la maladie de Creutzfeldt-Jakob.