biostudies-literaturede Zelicourt AAgence Nationale de la RechercheNIA NIH HHSFoundation for the National Institutes of HealthFondation de Francee12860https://www.ebi.ac.uk/biostudies/studies/S-EPMC9081905biostudies-literatureUnknown14(5)Duchenne muscular dystrophy (DMD) is characterized by progressive muscle degeneration. Two important deleterious features are a Ca²⁺ dysregulation linked to Ca²⁺ influxes associated with ryanodine receptor hyperactivation, and a muscular nicotinamide adenine dinucleotide (NAD⁺ ) deficit. Here, we identified that deletion in mdx mice of CD38, a NAD⁺ glycohydrolase-producing modulators of Ca²⁺ signaling, led to a fully restored heart function and structure, with skeletal muscle performance improvements, associated with a reduction in inflammation and senescence markers. Muscle NAD⁺ levels were also fully restored, while the levels of the two main products of CD38, nicotinamide and ADP-ribose, were reduced, in heart, diaphragm,EMBO molecular medicineCD38-NADase is a new major contributor to Duchenne muscular dystrophic phenotype.PMC9081905ANR‐10‐LABX‐33R01 AG058812AG58812ANR‐19‐CE14‐0031‐01NAD‐Heart # 17‐CE17‐0015‐0100086505ANR‐13‐BSV1‐0023‐01Dakouane-Giudicelli MPietri-Rouxel FBonay MPiquereau JChini ENLefebvre FChini CCSFogarty MJCancela JMForand ADe Jesus IBrisebard EMericskay MLaunay JMTarrago MGKaroui AZarrouki FSieck GCde la Porte SKashyap SMansart AMoog Sde Zelicourt AGomez AMFayssoil AfalseCD38-NADase is a new major contributor to Duchenne muscular dystrophic phenotype.Duchenne muscular dystrophy (DMD) is characterized by progressive muscle degeneration. Two important deleterious features are a Ca²⁺ dysregulation linked to Ca²⁺ influxes associated with ryanodine receptor hyperactivation, and a muscular nicotinamide adenine dinucleotide (NAD⁺ ) deficit. Here, we identified that deletion in mdx mice of CD38, a NAD⁺ glycohydrolase-producing modulators of Ca²⁺ signaling, led to a fully restored heart function and structure, with skeletal muscle performance improvements, associated with a reduction in inflammation and senescence markers. Muscle NAD⁺ levels were also fully restored, while the levels of the two main products of CD38, nicotinamide and ADP-ribose, were reduced, in heart, diaphragm,2022-01-01T00:00:00Z2022 May2025-04-19T12:09:13.824Z2025-02-19T00:55:35.589ZS-EPMC90819053529808910.15252/emmm.202012860