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Canadian Association of Neurosciences Review: Prion Protein and Prion Diseases: The Good and the Bad

Published online by Cambridge University Press:  02 December 2014

Malcolm J. Gains  and
Andrea C. LeBlanc
Malcolm J. Gains
Affiliation:
Department of Neurology and Neurosurgery, McGill University Département de pathologie et microbiologie, Faculté de médecine vétérinaire, University de Montréal, St. Hyacinthe, Québec, Canada
Andrea C. LeBlanc
Affiliation:
Department of Neurology and Neurosurgery, McGill University The Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montreal
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Abstract

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In the 1700's a strange new disease affecting sheep was recognized in Europe. The disease later became known as “Scrapie” and was the first of a family of similar diseases affecting a number of species that are now known as the Transmissible Spongiform Encephalopathies (TSEs). The appearance of a new disease in humans linked to the consumption of meat products from infected cattle has stimulated widespread public concern and scientific interest in the prion protein and related diseases. Nearly 300 years after the first report, these diseases still merit the descriptor “strange”. This family of diseases is characterized by a unique profile of histological changes, can be transmitted as inherited or acquired diseases, as well as apparent sporadic spontaneous generation of the disease. These diseases are believed by many, to be caused by a unique protein only infectious agent. The “prion protein” (PrPC), a term first coined by Stanley Prusiner in 1982 is crucial to the development of these diseases, apparently by acting as a substrate for an abnormal disease associated form. However, aside from being critical to the pathogenesis of the disease, the function of PrPC, which is expressed in all mammals, has defied definitive description. Several roles have been proposed on the basis of in vitro studies, however, thus far, in vivo confirmation has not been forthcoming. The biological features of PrPC also seem to be unusual. Numerous mouse models have been generated in an attempt to understand the pathogenesis of these diseases. This review summarizes the current state of histological features, the etiologic agent, the normal metabolism and the function of the prion protein, as well as the limitations of the mouse models.

Résumé:

RÉSUMÉ:

Au dix-huitième siècle, on s'est aperçu que les moutons étaient atteints d'une nouvelle maladie étrange en Europe. Cette maladie a plus tard été appelée « Scrapie » (la tremblante du mouton). C'était la première d'une famille de maladies similaires atteignant un certain nombre d'espèces animales qu'on désigne maintenant sous le vocable d'encéphalopathies spongiformes transmissibles (EST). L'apparition chez l'humain d'une nouvelle maladie liée à la consommation de produits carnés provenant d'animaux infectés a suscité beaucoup d'inquiétude dans la population et d'intérêt scientifique pour la protéine prion et les maladies qui y sont associées. Environ 300 ans après que les premiers cas aient été rapportés, ces maladies méritent toujours d'être décrites comme « étranges ». Cette famille de maladies est caractérisée par un profil unique de changements histologiques, elles peuvent être transmises de façon héréditaires ou être acquises et on peut observer des cas sporadiques dont la génération semble spontanée. Plusieurs croient que ces maladies sont causées par un agent infectieux de nature uniquement protéique. La « protéine prion » (PrPc), une expression utilisée pour la première fois par Stanley Prusiner en 1982, est cruciale pour le développement de ces maladies agissant, semble-t-il, comme substrat à une forme anormale de la protéine associée à la maladie. Cependant, la fonction de PrPc, une protéine qui est exprimée chez tous les mammifères, n'a pas encore pu être décrite définitivement, en dehors du fait qu'elle est cruciale dans la pathogenèse de la maladie. On a proposé plusieurs rôles pour la PrPc sur la base des études in vitro, mais aucun n'a jamais été confirmé in vivo. Les caractéristiques biologiques de la PrPc semblent également inusitées. Plusieurs modèles de souris ont été créés afin d'essayer de comprendre la pathogenèse de ces maladies. Cette revue fait le sommaire des connaissances actuelles sur les caractéristiques histologiques, l'agent étiologique, le métabolisme normal et la fonction de la protéine prion, de même que les limites des modèles chez la souris.

Type
Review Article
Information
Canadian Journal of Neurological Sciences , Volume 34 , Issue 2 , May 2007 , pp. 126 - 145
Copyright
Copyright © The Canadian Journal of Neurological 2007

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