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.

Scaricamazza, S., Salvatori, I., Giacovazzo, G., Loeffler, J.p., Renè, F., Rosina, M., et al. (2020). Skeletal-Muscle Metabolic Reprogramming in ALS-SOD1G93A Mice Predates Disease Onset and Is A Promising Therapeutic Target. ISCIENCE, 23(5) [10.1016/j.isci.2020.101087].

Skeletal-Muscle Metabolic Reprogramming in ALS-SOD1G93A Mice Predates Disease Onset and Is A Promising Therapeutic Target

Scaricamazza, Silvia;Giacovazzo, Giacomo;Rosina, Marco;Rossi, Simona;
2020-01-01

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.
2020
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10
English
Con Impact Factor ISI
Cellular Neuroscience
Drugs
Molecular Neuroscience
Scaricamazza, S., Salvatori, I., Giacovazzo, G., Loeffler, J.p., Renè, F., Rosina, M., et al. (2020). Skeletal-Muscle Metabolic Reprogramming in ALS-SOD1G93A Mice Predates Disease Onset and Is A Promising Therapeutic Target. ISCIENCE, 23(5) [10.1016/j.isci.2020.101087].
Scaricamazza, S; Salvatori, I; Giacovazzo, G; Loeffler, Jp; Renè, F; Rosina, M; Quessada, C; Proietti, D; Heil, C; Rossi, S; Battistini, S; Giannini,...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/367683
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