Back to Search
Start Over
Prion diseases disrupt glutamate/glutamine metabolism in skeletal muscle.
- Source :
-
PLoS pathogens [PLoS Pathog] 2024 Sep 11; Vol. 20 (9), pp. e1012552. Date of Electronic Publication: 2024 Sep 11 (Print Publication: 2024). - Publication Year :
- 2024
-
Abstract
- In prion diseases (PrDs), aggregates of misfolded prion protein (PrPSc) accumulate not only in the brain but also in extraneural organs. This raises the question whether prion-specific pathologies arise also extraneurally. Here we sequenced mRNA transcripts in skeletal muscle, spleen and blood of prion-inoculated mice at eight timepoints during disease progression. We detected gene-expression changes in all three organs, with skeletal muscle showing the most consistent alterations. The glutamate-ammonia ligase (GLUL) gene exhibited uniform upregulation in skeletal muscles of mice infected with three distinct scrapie prion strains (RML, ME7, and 22L) and in victims of human sporadic Creutzfeldt-Jakob disease. GLUL dysregulation was accompanied by changes in glutamate/glutamine metabolism, leading to reduced glutamate levels in skeletal muscle. None of these changes were observed in skeletal muscle of humans with amyotrophic lateral sclerosis, Alzheimer's disease, or dementia with Lewy bodies, suggesting that they are specific to prion diseases. These findings reveal an unexpected metabolic dimension of prion infections and point to a potential role for GLUL dysregulation in the glutamate/glutamine metabolism in prion-affected skeletal muscle.<br />Competing Interests: The authors have declared that no competing interests exist.<br /> (Copyright: © 2024 Caredio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Subjects :
- Animals
Mice
Humans
Glutamate-Ammonia Ligase metabolism
Creutzfeldt-Jakob Syndrome metabolism
Creutzfeldt-Jakob Syndrome pathology
Creutzfeldt-Jakob Syndrome genetics
Female
Mice, Inbred C57BL
Muscle, Skeletal metabolism
Muscle, Skeletal pathology
Glutamine metabolism
Glutamic Acid metabolism
Prion Diseases metabolism
Prion Diseases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7374
- Volume :
- 20
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- PLoS pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 39259763
- Full Text :
- https://doi.org/10.1371/journal.ppat.1012552