[Molecular bases of prion diseases].
Prion diseases are transmissible neurodegenerative conditions that include Creutzfeldt-Jakob disease (CJD) in humans and bovine spongiform encephalopathy and scrapie in animals. The normal cellular prion protein (PrP(c)) is a membrane sialoglycoprotein of unknown function having the unique property of adopting an abnormal tertiary conformation. The pathological conformer (PrP(sc)) would be the agent of transmissible spongiform encephalopathies or prion diseases. Prion propagation involves recruitment of host cellular prion protein, primarily of alpha-helical structure, into a disease-specific isoform rich in beta-sheet structure. The existence of multiple prion strains has been difficult to explain in terms of a protein-only infectious agent, but recent studies suggest that strain specific phenotypes can be encoded by different prion protein conformations and glycosylation patterns. It is an intriguing proposition that the post-translational modifications alone, or in combination with amino acid changes, play dominant roles in the pathogenic transformation of PrP(c) to PrP(sc). Prion diseases are unique in that they comprise sporadic, genetic (autosomal dominant inheritance), and iatrogenically or environmentally acquired forms. Point mutations in the prion protein gene lead to neurodegenerative disease.
Rać
Monika
M
Zakład Biochemii, Pomorskiej Akademii Medycznej, al. Powstańców Wielkopolskich 72, 70-111 Szczecin.
Rać
Michał
M
D000818:Animals; D019286:Endopeptidase K / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D009154:Mutation; D018621:PrPC Proteins / Q000737:chemistry*; D017096:Prion Diseases / Q000235:genetics*; D011487:Protein Conformation
D018621:PrPC Proteins; D019286:Endopeptidase K