Cystatin F is a biomarker of prion pathogenesis in mice.
Misfolding of the cellular prion protein (PrPC) into the scrapie prion protein (PrPSc) results in progressive, fatal, transmissible neurodegenerative conditions termed prion diseases. Experimental and epidemiological evidence point toward a protracted, clinically silent phase in prion diseases, yet...
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171923&type=printable |
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| author | Mario Nuvolone Nicolas Schmid Gino Miele Silvia Sorce Rita Moos Christian Schori Roger R Beerli Monika Bauer Philippe Saudan Klaus Dietmeier Ingolf Lachmann Michael Linnebank Roland Martin Ulf Kallweit Veronika Kana Elisabeth J Rushing Herbert Budka Adriano Aguzzi |
| author_facet | Mario Nuvolone Nicolas Schmid Gino Miele Silvia Sorce Rita Moos Christian Schori Roger R Beerli Monika Bauer Philippe Saudan Klaus Dietmeier Ingolf Lachmann Michael Linnebank Roland Martin Ulf Kallweit Veronika Kana Elisabeth J Rushing Herbert Budka Adriano Aguzzi |
| author_sort | Mario Nuvolone |
| collection | DOAJ |
| description | Misfolding of the cellular prion protein (PrPC) into the scrapie prion protein (PrPSc) results in progressive, fatal, transmissible neurodegenerative conditions termed prion diseases. Experimental and epidemiological evidence point toward a protracted, clinically silent phase in prion diseases, yet there is no diagnostic test capable of identifying asymptomatic individuals incubating prions. In an effort to identify early biomarkers of prion diseases, we have compared global transcriptional profiles in brains from pre-symptomatic prion-infected mice and controls. We identified Cst7, which encodes cystatin F, as the most strongly upregulated transcript in this model. Early and robust upregulation of Cst7 mRNA levels and of its cognate protein was validated in additional mouse models of prion disease. Surprisingly, we found no significant increase in cystatin F levels in both cerebrospinal fluid or brain parenchyma of patients with Creutzfeldt-Jakob disease compared to Alzheimer's disease or non-demented controls. Our results validate cystatin F as a useful biomarker of early pathogenesis in experimental models of prion disease, and point to unexpected species-specific differences in the transcriptional responses to prion infections. |
| format | Article |
| id | doaj-art-179c400da9454da8a9b5bfc1f0d4bf9c |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-179c400da9454da8a9b5bfc1f0d4bf9c2025-08-20T02:45:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01122e017192310.1371/journal.pone.0171923Cystatin F is a biomarker of prion pathogenesis in mice.Mario NuvoloneNicolas SchmidGino MieleSilvia SorceRita MoosChristian SchoriRoger R BeerliMonika BauerPhilippe SaudanKlaus DietmeierIngolf LachmannMichael LinnebankRoland MartinUlf KallweitVeronika KanaElisabeth J RushingHerbert BudkaAdriano AguzziMisfolding of the cellular prion protein (PrPC) into the scrapie prion protein (PrPSc) results in progressive, fatal, transmissible neurodegenerative conditions termed prion diseases. Experimental and epidemiological evidence point toward a protracted, clinically silent phase in prion diseases, yet there is no diagnostic test capable of identifying asymptomatic individuals incubating prions. In an effort to identify early biomarkers of prion diseases, we have compared global transcriptional profiles in brains from pre-symptomatic prion-infected mice and controls. We identified Cst7, which encodes cystatin F, as the most strongly upregulated transcript in this model. Early and robust upregulation of Cst7 mRNA levels and of its cognate protein was validated in additional mouse models of prion disease. Surprisingly, we found no significant increase in cystatin F levels in both cerebrospinal fluid or brain parenchyma of patients with Creutzfeldt-Jakob disease compared to Alzheimer's disease or non-demented controls. Our results validate cystatin F as a useful biomarker of early pathogenesis in experimental models of prion disease, and point to unexpected species-specific differences in the transcriptional responses to prion infections.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171923&type=printable |
| spellingShingle | Mario Nuvolone Nicolas Schmid Gino Miele Silvia Sorce Rita Moos Christian Schori Roger R Beerli Monika Bauer Philippe Saudan Klaus Dietmeier Ingolf Lachmann Michael Linnebank Roland Martin Ulf Kallweit Veronika Kana Elisabeth J Rushing Herbert Budka Adriano Aguzzi Cystatin F is a biomarker of prion pathogenesis in mice. PLoS ONE |
| title | Cystatin F is a biomarker of prion pathogenesis in mice. |
| title_full | Cystatin F is a biomarker of prion pathogenesis in mice. |
| title_fullStr | Cystatin F is a biomarker of prion pathogenesis in mice. |
| title_full_unstemmed | Cystatin F is a biomarker of prion pathogenesis in mice. |
| title_short | Cystatin F is a biomarker of prion pathogenesis in mice. |
| title_sort | cystatin f is a biomarker of prion pathogenesis in mice |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171923&type=printable |
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