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

Silvia Scaricamazza, Illari Salvatori, Giacomo Giacovazzo, Jean Philippe Loeffler, Frederique Renè, Marco Rosina, Cyril Quessada, Daisy Proietti, Constantin Heil, Simona Rossi, Stefania Battistini, Fabio Giannini, Nila Volpi, Frederik J. Steyn, Shyuan T. Ngo, Elisabetta Ferraro, Luca Madaro, Roberto Coccurello, Cristiana Valle, Alberto Ferri

Research output: Contribution to journalArticlepeer-review

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 SOD1G93A 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 SOD1G93A mice with Ranolazine, an FDA-approved inhibitor of fatty acid β-oxidation, led to a decrease in energy expenditure in symptomatic SOD1G93A mice, and this occurred in parallel with a robust, albeit temporary, recovery of the pathological phenotype.

Original languageEnglish
Article number101087
JournaliScience
Volume23
Issue number5
DOIs
Publication statusPublished - May 22 2020

Keywords

  • Cellular Neuroscience
  • Drugs
  • Molecular Neuroscience

ASJC Scopus subject areas

  • General

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