Patients with ALS show, in addition to the loss of motor neurons in the spinal cord, brainstem, and cerebral cortex, an abnormal depletion of energy stores alongside hypermetabolism. In this study, we show that bioenergetic defects and muscle remodeling occur in skeletal muscle of the SOD1(G93A) mouse model of ALS mice prior to disease onset and before the activation of muscle denervation markers, respectively. These changes in muscle physiology were followed by an increase in energy expenditure unrelated to physical activity. Finally, chronic treatment of SOD1(G93A) mice with Ranolazine, an FDA-approved inhibitor of fatty acid beta-oxidation, led to a decrease in energy expenditure in symptomatic SOD1(G93A) mice, and this occurred in parallel with a robust, albeit temporary, recovery of the pathological phenotype.
Skeletal-Muscle Metabolic Reprogramming in ALS-SOD1(G93A) Mice Predates Disease Onset and Is A Promising Therapeutic Target
Giacovazzo, Giacomo;Rossi, Simona;Coccurello, Roberto;Valle, Cristiana;Ferri, Alberto
2020
Abstract
Patients with ALS show, in addition to the loss of motor neurons in the spinal cord, brainstem, and cerebral cortex, an abnormal depletion of energy stores alongside hypermetabolism. In this study, we show that bioenergetic defects and muscle remodeling occur in skeletal muscle of the SOD1(G93A) mouse model of ALS mice prior to disease onset and before the activation of muscle denervation markers, respectively. These changes in muscle physiology were followed by an increase in energy expenditure unrelated to physical activity. Finally, chronic treatment of SOD1(G93A) mice with Ranolazine, an FDA-approved inhibitor of fatty acid beta-oxidation, led to a decrease in energy expenditure in symptomatic SOD1(G93A) mice, and this occurred in parallel with a robust, albeit temporary, recovery of the pathological phenotype.File | Dimensione | Formato | |
---|---|---|---|
prod_425197-doc_151665.pdf
accesso aperto
Descrizione: Skeletal-Muscle Metabolic Reprogramming in ALS-SOD1(G93A) Mice Predates Disease Onset and Is A Promising Therapeutic Target
Tipologia:
Versione Editoriale (PDF)
Licenza:
Creative commons
Dimensione
5.59 MB
Formato
Adobe PDF
|
5.59 MB | Adobe PDF | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.