Objective: To study the possible effect of tetracycline on protease-resistant activity in vitro and infectivity in vivo of a scrapie strain 263K.
Methods: Scrapie pathogens were incubated with tetracycline at different concentrations for various periods of time and protease-resistant PrP signals were evaluated with proteinase K-treatment and Western blots. The preparations treated with tetracycline were intracerebrally inoculated into golden hamsters and typical TSE manifestations were noted. PrPSc in brain tissues of the infected animals was detected by PrP specific Western blot assays.
Results: Protease-resistant PrP was significantly reduced in or removed from the preparations treated with tetracycline in a dose-dependant manner. Compared with the control group after incubated for 53.75 +/- 0.50 days, the preparations treated with 5 mmol/L and 20 mmol/L tetracycline prolonged the incubation time of 61.5 +/- 1.73 and 59.5 +/- 0.58 days (P < 0.05).
Conclusion: Treatment of scrapie pathogen 263K with tetracycline reduces or removes its protease-resistant activity in vitro.
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Viruses
December 2024
Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou 225012, China.
The ongoing global health crisis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates the continuous development of innovative vaccine strategies, especially in light of emerging viral variants that could undermine the effectiveness of existing vaccines. In this study, we developed a recombinant virus-like particle (VLP) vaccine based on the Newcastle Disease Virus (NDV) platform, displaying a stabilized prefusion form of the SARS-CoV-2 spike (S) protein. This engineered S protein includes two proline substitutions (K986P, V987P) and a mutation at the cleavage site (RRAR to QQAQ), aimed at enhancing both its stability and immunogenicity.
View Article and Find Full Text PDFNat Commun
December 2024
Institute of Physiological Chemistry, Faculty of Medicine, Philipps University of Marburg, Marburg, Germany.
ADMET DMPK
November 2024
Medical Bionanotechnology, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Chettinad Health City, Kelambakkam, Chennai-603103, India.
Background And Purpose: Amyloidosis is a group of diseases including diabetes type II and neurological disorders, such as Alzheimer's disease, Parkinson's disease, prion disease, etc., where a common trait is observed; accumulation of misfolded protein at different parts of the body, especially the brain which manifests the typical symptoms like dementia, movement disorders, etc. These misfolded proteins, named amyloids, are protease resistant and thus it becomes difficult to manage these diseases in vivo.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Rocky Mountain Laboratories, Laboratory of Neurological Infections and Immunity, National Institute of Allergy & Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
The mammalian prion protein can form infectious, nonnative, and protease resistant aggregates (PrP), which cause lethal prion diseases like human Creutzfeldt-Jakob disease. PrP seeds the formation of new infectious prions by interacting with and triggering the refolding of the normally soluble mammalian prion protein, PrP, into more PrP. Refolding of misfolded proteins in the cell is carried out by molecular chaperones such as Grp78.
View Article and Find Full Text PDFEur J Med Chem
October 2023
Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA. Electronic address:
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