129648 20241125101133.0 doi 10.3390/ijms242115783 sideral 135871 ART-2023-135871 eng Gonzalo-Gobernado, Rafael Repaglinide induces 003726 processing and neuroprotection in transgenic SOD1G93A mice 2023 Access copy available to the general public Unrestricted The interaction of the activating transcription factor 6 (ATF6), a key effector of the unfolded protein response (UPR) in the endoplasmic reticulum, with the neuronal calcium sensor Downstream Regulatory Element Antagonist Modulator (DREAM) is a potential therapeutic target in neurodegeneration. Modulation of the ATF6–DREAM interaction with repaglinide (RP) induced neuroprotection in a model of Huntington’s disease. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with no cure, characterized by the progressive loss of motoneurons resulting in muscle denervation, atrophy, paralysis, and death. The aim of this work was to investigate the potential therapeutic significance of DREAM as a target for intervention in ALS. We found that the expression of the DREAM protein was reduced in the spinal cord of SOD1G93A mice compared to wild-type littermates. RP treatment improved motor strength and reduced the expression of the ALS progression marker collagen type XIXα1 (Col19α1 mRNA) in the quadriceps muscle in SOD1G93A mice. Moreover, treated SOD1G93A mice showed reduced motoneuron loss and glial activation and increased ATF6 processing in the spinal cord. These results indicate that the modulation of the DREAM–ATF6 interaction ameliorates ALS symptoms in SOD1G93A mice. info:eu-repo/grantAgreement/ES/ISCIII/FEDER/PI21-00372 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 4.9 2023 BIOCHEMISTRY & MOLECULAR BIOLOGY 66 / 313 = 0.211 2023 Q1 T1 CHEMISTRY, MULTIDISCIPLINARY 68 / 231 = 0.294 2023 Q2 T1 1.179 2023 Medicine (miscellaneous) 2023 Q1 Physical and Theoretical Chemistry 2023 Q1 Computer Science Applications 2023 Q1 Inorganic Chemistry 2023 Q1 Spectroscopy 2023 Q1 Organic Chemistry 2023 Q1 Molecular Biology 2023 Q2 Catalysis 2023 Q2 8.1 2023 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Moreno-Martínez, Laura Universidad de Zaragoza (orcid)0000-0002-7277-4318 González, Paz Dopazo, Xose Manuel Calvo, Ana Cristina Universidad de Zaragoza (orcid)0000-0001-5193-7782 Pidal-Ladrón de Guevara, Isabel Seisdedos, Elisa Díaz-Muñoz, Rodrigo Mellström, Britt Osta, Rosario Universidad de Zaragoza (orcid)0000-0001-5687-6704 Naranjo, José Ramón 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 24, 21 (2023), 15783 [16 pp.] Int. j. mol. sci. International Journal of Molecular Sciences 1661-6596 3960470 http://zaguan.unizar.es/record/129648/files/texto_completo.pdf Versión publicada 2848281 http://zaguan.unizar.es/record/129648/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:129648 articulos driver 2024-11-22-11:59:34 ARTICLE