162125 20251017144628.0 doi 10.1016/j.ijbiomac.2025.145645 sideral 144733 ART-2025-144733 eng Rodriguez-Romano, Ana Injectable 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 2025 Access copy available to the general public Unrestricted Amyotrophic 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. info:eu-repo/grantAgreement/ES/ISCIII/CB06-01-1026 info:eu-repo/grantAgreement/ES/AEI/MICNN/PID2021-126012OB-I00 info:eu-repo/semantics/openAccess by-nc-nd https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Gonzalez-Valdivieso, Juan Moreno-Martinez, Laura Universidad de Zaragoza (orcid)0000-0002-7277-4318 Vázquez Costa, Juan Francisco Osta, Rosario Universidad de Zaragoza (orcid)0000-0001-5687-6704 Rico, Patricia 1001 420 Universidad de Zaragoza Dpto. Anatom.,Embri.Genét.Ani. Área Genética 1012 315 Universidad de Zaragoza Dpto. Farmac.Fisiol.y Med.L.F. Área Farmacología 319 (2025), 145645 [16 pp.] Int. j. biol. macromol. International journal of biological macromolecules 0141-8130 11636462 http://zaguan.unizar.es/record/162125/files/texto_completo.pdf Versión publicada 2374530 http://zaguan.unizar.es/record/162125/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:162125 articulos driver 2025-10-17-14:25:00 ARTICLE