The prion protein is a normal cellular glycoprotein which, after conversion to a protease resistant pathogenic form appears to be the major, if not the only, component of the infectious agent known as the prion. Numerous strains of prions, differing in their incubation period and neuropathology, have been isolated in the same host genotype, indicating that prions carry information which is independent from the host. Molecular analysis of prion strains has recently focused on human prion diseases and support the view that the prion protein can specify disease phenotypes by differences in its conformation and glycosylation. The observation that approximately 10-15% of all human prion diseases are familiar and result from mutations in the prion protein gene provided a basis for pursuing the factors that favor, or result in, the de novo conversion of the prion protein to a pathogenic form. A cell culture model was established to study the effects of the pathogenic mutations on the metabolism of the mutant prion protein. One of the consistent changes found as a result of the pathogenic mutations clustered in the region of post-translational modification was an alteration of the glycoisoform ratio; an observation that also applies to prion protein derived from prion diseased brain samples.

Chapter 5: Inherited prion disease: molecular pathology and cell models.

ZANUSSO, Gianluigi;
1999-01-01

Abstract

The prion protein is a normal cellular glycoprotein which, after conversion to a protease resistant pathogenic form appears to be the major, if not the only, component of the infectious agent known as the prion. Numerous strains of prions, differing in their incubation period and neuropathology, have been isolated in the same host genotype, indicating that prions carry information which is independent from the host. Molecular analysis of prion strains has recently focused on human prion diseases and support the view that the prion protein can specify disease phenotypes by differences in its conformation and glycosylation. The observation that approximately 10-15% of all human prion diseases are familiar and result from mutations in the prion protein gene provided a basis for pursuing the factors that favor, or result in, the de novo conversion of the prion protein to a pathogenic form. A cell culture model was established to study the effects of the pathogenic mutations on the metabolism of the mutant prion protein. One of the consistent changes found as a result of the pathogenic mutations clustered in the region of post-translational modification was an alteration of the glycoisoform ratio; an observation that also applies to prion protein derived from prion diseased brain samples.
1999
9781898486077
Prion; post-translational modification; molecular phenotype; FFI; prion strains; conformation
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/333213
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