The Prion Protein Preference of Sporadic Creutzfeldt-Jakob Disease Subtypes
| Autor: | Steven J. Collins, Genevieve M Klug, Andrew F. Hill, Jeremy M. Welton, Alison Boyd, Victoria A. Lawson, Helen M. J. Klemm, Colin L. Masters |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Protein Folding animal diseases Disease Biology Biochemistry Creutzfeldt-Jakob Syndrome Mice mental disorders Animals Humans PrPC Proteins Prion protein Codon Molecular Biology Gene Brain Chemistry Mice Knockout Genetics Mice Inbred BALB C Polymorphism Genetic Molecular mass Brain Molecular Bases of Disease Cell Biology Sporadic Creutzfeldt-Jakob disease Phenotype Virology nervous system diseases Female Protein folding |
| Zdroj: | Journal of Biological Chemistry. 287:36465-36472 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m112.368803 |
| Popis: | Sporadic Creutzfeldt-Jakob disease (CJD) is the most prevalent manifestation of the transmissible spongiform encephalopathies or prion diseases affecting humans. The disease encompasses a spectrum of clinical phenotypes that have been correlated with molecular subtypes that are characterized by the molecular mass of the protease-resistant fragment of the disease-related conformation of the prion protein and a polymorphism at codon 129 of the gene encoding the prion protein. A cell-free assay of prion protein misfolding was used to investigate the ability of these sporadic CJD molecular subtypes to propagate using brain-derived sources of the cellular prion protein (PrP(C)). This study confirmed the presence of three distinct sporadic CJD molecular subtypes with PrP(C) substrate requirements that reflected their codon 129 associations in vivo. However, the ability of a sporadic CJD molecular subtype to use a specific PrP(C) substrate was not determined solely by codon 129 as the efficiency of prion propagation was also influenced by the composition of the brain tissue from which the PrP(C) substrate was sourced, thus indicating that nuances in PrP(C) or additional factors may determine sporadic CJD subtype. The results of this study will aid in the design of diagnostic assays that can detect prion disease across the diversity of sporadic CJD subtypes. |
| Databáze: | OpenAIRE |
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