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Citations to this article

Prion disease tempo determined by host-dependent substrate reduction
Charles E. Mays, … , David Westaway, Jiri G. Safar
Charles E. Mays, … , David Westaway, Jiri G. Safar
Published January 16, 2014
Citation Information: J Clin Invest. 2014;124(2):847-858. https://doi.org/10.1172/JCI72241.
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Research Article Neuroscience Article has an altmetric score of 57

Prion disease tempo determined by host-dependent substrate reduction

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Abstract

The symptoms of prion infection can take years or decades to manifest following the initial exposure. Molecular markers of prion disease include accumulation of the misfolded prion protein (PrPSc), which is derived from its cellular precursor (PrPC), as well as downregulation of the PrP-like Shadoo (Sho) glycoprotein. Given the overlapping cellular environments for PrPC and Sho, we inferred that PrPC levels might also be altered as part of a host response during prion infection. Using rodent models, we found that, in addition to changes in PrPC glycosylation and proteolytic processing, net reductions in PrPC occur in a wide range of prion diseases, including sheep scrapie, human Creutzfeldt-Jakob disease, and cervid chronic wasting disease. The reduction in PrPC results in decreased prion replication, as measured by the protein misfolding cyclic amplification technique for generating PrPSc in vitro. While PrPC downregulation is not discernible in animals with unusually short incubation periods and high PrPC expression, slowly evolving prion infections exhibit downregulation of the PrPC substrate required for new PrPSc synthesis and as a receptor for pathogenic signaling. Our data reveal PrPC downregulation as a previously unappreciated element of disease pathogenesis that defines the extensive, presymptomatic period for many prion strains.

Authors

Charles E. Mays, Chae Kim, Tracy Haldiman, Jacques van der Merwe, Agnes Lau, Jing Yang, Jennifer Grams, Michele A. Di Bari, Romolo Nonno, Glenn C. Telling, Qingzhong Kong, Jan Langeveld, Debbie McKenzie, David Westaway, Jiri G. Safar

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Total citations by year

Year: 2025 2024 2022 2021 2020 2019 2018 2017 2016 2015 2014 Total
Citations: 2 4 8 2 6 6 4 6 3 7 1 49
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2015 (7)

Title and authors Publication Year
Octarepeat region flexibility impacts prion function, endoproteolysis and disease manifestation
A Lau, A McDonald, N Daude, CE Mays, ED Walter, R Aglietti, RC Mercer, S Wohlgemuth, J der Merwe, J Yang, H Gapeshina, C Kim, J Grams, B Shi, H Wille, A Balachandran, G Schmitt-Ulms, JG Safar, GL Millhauser, D Westaway
EMBO Molecular Medicine 2015
Rapidly progressive Alzheimer's disease features distinct structures of amyloid- 
ML Cohen, C Kim, T Haldiman, M ElHag, P Mehndiratta, T Pichet, F Lissemore, M Shea, Y Cohen, W Chen, J Blevins, BS Appleby, K Surewicz, WK Surewicz, M Sajatovic, C Tatsuoka, S Zhang, P Mayo, M Butkiewicz, JL Haines, AJ Lerner, JG Safar
Brain 2015
Double-Edge Sword of Sustained ROCK Activation in Prion Diseases through Neuritogenesis Defects and Prion Accumulation
A Alleaume-Butaux, S Nicot, M Pietri, A Baudry, C Dakowski, P Tixador, H Ardila-Osorio, AM Haeberlé, Y Bailly, JM Peyrin, JM Launay, O Kellermann, B Schneider, P Lingor
PLoS pathogens 2015
Early Generation of New PrPSc on Blood Vessels after Brain Microinjection of Scrapie in Mice
B Chesebro, J Striebel, A Rangel, K Phillips, A Hughson, B Caughey, B Race
mBio 2015
Prion Infectivity Plateaus and Conversion to Symptomatic Disease Originate from Falling Precursor Levels and Increased Levels of Oligomeric PrP Sc Species
CE Mays, J der Merwe, C Kim, T Haldiman, D McKenzie, JG Safar, D Westaway, BW Caughey
Journal of virology 2015
The prion protein constitutively controls neuronal store-operated Ca2+ entry through Fyn kinase
AD Mario, A Castellani, C Peggion, ML Massimino, D Lim, AF Hill, MC Sorgato, A Bertoli
Frontiers in cellular neuroscience 2015
Neuroprotective properties of the PrP-like Shadoo glycoprotein assessed in the middle cerebral artery occlusion model of ischemia
N Daude, H Gapeshina, B Dong, I Winship, D Westaway
Prion 2015

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