000162125 001__ 162125 000162125 005__ 20251017144628.0 000162125 0247_ $$2doi$$a10.1016/j.ijbiomac.2025.145645 000162125 0248_ $$2sideral$$a144733 000162125 037__ $$aART-2025-144733 000162125 041__ $$aeng 000162125 100__ $$aRodriguez-Romano, Ana 000162125 245__ $$aInjectable borax-loaded alginate hydrogels reduce muscle atrophy, modulate inflammation, and promote neuroprotection in the SOD1G93A mouse model of ALS through mechanisms involving IGF–Akt–mTOR signaling 000162125 260__ $$c2025 000162125 5060_ $$aAccess copy available to the general public$$fUnrestricted 000162125 5203_ $$aAmyotrophic Lateral Sclerosis (ALS) is a prevalent condition characterized by motor neuron loss and skeletal muscle paralysis. Despite being associated to mutations in over 40 genes, its etiology remains elusive without a cure or effective treatment. ALS, historically considered a motor neuron disease, is defined today as a multisystem disorder involving non-neuronal cell types, including early muscle pathology independent of motor neuron degeneration (dying back hypothesis), thus skeletal muscle actively contributes to disease pathology, making it a viable therapeutic target for ALS. Our previous research has shown that boron transporter NaBC1 (encoded by the SLC4A11 gene), after activation co-localizes with integrins and growth factor receptors synergistically enhancing muscle repair. Here we investigate the effects of injectable alginate-based hydrogels for controlled local borax release in Amyotrophic Lateral Sclerosis muscle. Treated mice showed improved motor function, prolonged survival, and activation of essential muscle metabolic pathways, leading to enhanced muscle repair and reduced atrophy and inflammation. Interestingly, local muscle repair activation provided retrograde neuroprotection by preserving motor neurons and reducing neuro-inflammation. This study highlights the role of muscle tissue in ALS pathology, supporting its targeting with NaBC1-based therapies for muscle regeneration. 000162125 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/CB06-01-1026$$9info:eu-repo/grantAgreement/ES/AEI/MICNN/PID2021-126012OB-I00 000162125 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es 000162125 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000162125 700__ $$aGonzalez-Valdivieso, Juan 000162125 700__ $$0(orcid)0000-0002-7277-4318$$aMoreno-Martinez, Laura$$uUniversidad de Zaragoza 000162125 700__ $$aVázquez Costa, Juan Francisco 000162125 700__ $$0(orcid)0000-0001-5687-6704$$aOsta, Rosario$$uUniversidad de Zaragoza 000162125 700__ $$aRico, Patricia 000162125 7102_ $$11001$$2420$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Genética 000162125 7102_ $$11012$$2315$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Farmacología 000162125 773__ $$g319 (2025), 145645 [16 pp.]$$pInt. j. biol. macromol.$$tInternational journal of biological macromolecules$$x0141-8130 000162125 8564_ $$s11636462$$uhttps://zaguan.unizar.es/record/162125/files/texto_completo.pdf$$yVersión publicada 000162125 8564_ $$s2374530$$uhttps://zaguan.unizar.es/record/162125/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000162125 909CO $$ooai:zaguan.unizar.es:162125$$particulos$$pdriver 000162125 951__ $$a2025-10-17-14:25:00 000162125 980__ $$aARTICLE