PrP(ST), a soluble, protease resistant and truncated PrP form features in the pathogenesis of a genetic prion disease
| العنوان: | PrP(ST), a soluble, protease resistant and truncated PrP form features in the pathogenesis of a genetic prion disease |
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| المؤلفون: | Michal Mizrahi, Orli Binyamin, Kati Frid, Yael Friedman-Levi, Ruth Gabizon |
| المصدر: | PLoS ONE, Vol 8, Iss 7, p e69583 (2013) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Mouse, Clinical Research Design, animal diseases, Mutant, lcsh:Medicine, Scrapie, Biology, medicine.disease_cause, Biochemistry, Prion Diseases, Pathogenesis, Model Organisms, Diagnostic Medicine, Pathology, medicine, Animal Models of Disease, lcsh:Science, Neuropathology, Mutation, Multidisciplinary, lcsh:R, Proteins, Heterozygote advantage, Animal Models, Creutzfeldt-Jakob Syndrome, Virology, Human genetics, nervous system diseases, Infectious Diseases, Neurology, Membrane protein, Anatomical Pathology, Medicine, Dementia, lcsh:Q, Molecular Pathology, Research Article, General Pathology |
| الوصف: | While the conversion of PrP(C) into PrP(Sc) in the transmissible form of prion disease requires a preexisting PrP(Sc) seed, in genetic prion disease accumulation of disease related PrP could be associated with biochemical and metabolic modifications resulting from the designated PrP mutation. To investigate this possibility, we looked into the time related changes of PrP proteins in the brains of TgMHu2ME199K/wt mice, a line modeling for heterozygous genetic prion disease linked to the E200K PrP mutation. We found that while oligomeric entities of mutant E199KPrP exist at all ages, aggregates of wt PrP in the same brains presented only in advanced disease, indicating a late onset conversion process. We also show that most PK resistant PrP in TgMHu2ME199K mice is soluble and truncated (PrP(ST)), a pathogenic form never before associated with prion disease. We next looked into brain samples from E200K patients and found that both PK resistant PrPs, PrP(ST) as in TgMHu2ME199K mice, and "classical" PrP(Sc) as in infectious prion diseases, coincide in the patient's post mortem brains. We hypothesize that aberrant metabolism of mutant PrPs may result in the formation of previously unknown forms of the prion protein and that these may be central for the fatal outcome of the genetic prion condition. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c730815438015fbf4d4f8749d767bf36Test http://europepmc.org/articles/PMC3724911?pdf=renderTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c730815438015fbf4d4f8749d767bf36 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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