Prion diseases disrupt glutamate/glutamine metabolism in skeletal muscle
2024; Public Library of Science; Volume: 20; Issue: 9 Linguagem: Inglês
10.1371/journal.ppat.1012552
ISSN1553-7374
AutoresDavide Caredio, Maruša Koderman, Karl Frontzek, Silvia Sorce, Mario Nuvolone, Juliane Bremer, Giovanni Mariutti, Petra Schwarz, Lidia Madrigal, Milena Mitrović, Stefano Sellitto, Nathalie Streichenberger, Claudia Scheckel, Adriano Aguzzi,
Tópico(s)Alcoholism and Thiamine Deficiency
ResumoIn prion diseases (PrDs), aggregates of misfolded prion protein (PrP Sc ) 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.
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