Utrophin modulator drugs as potential therapies for Duchenne and Becker muscular dystrophies
dc.contributor.author | Soblechero-Martín, Patricia | |
dc.contributor.author | López-Martínez, Andrea | |
dc.contributor.author | De la Puente-Ovejero, Laura | |
dc.contributor.author | Vallejo Illarramendi, Ainara | |
dc.contributor.author | Arechavala-Gomeza, Virginia | |
dc.date.accessioned | 2021-12-23T11:07:05Z | |
dc.date.available | 2021-12-23T11:07:05Z | |
dc.date.issued | 2021-10 | |
dc.identifier.citation | Neuropathology and Applied Neurobiology 47(6) : 711-723 (2021) | es_ES |
dc.identifier.issn | 0305-1846 | |
dc.identifier.issn | 1365-2990 | |
dc.identifier.uri | http://hdl.handle.net/10810/54726 | |
dc.description.abstract | Utrophin is an autosomal paralogue of dystrophin, a protein whose deficit causes Duchenne and Becker muscular dystrophies (DMD/BMD). Utrophin is naturally overexpressed at the sarcolemma of mature dystrophin-deficient fibres in DMD and BMD patients as well as in the mdx Duchenne mouse model. Dystrophin and utrophin can co-localise in human foetal muscle, in the dystrophin-competent fibres from DMD/BMD carriers, and revertant fibre clusters in biopsies from DMD patients. These findings suggest that utrophin overexpression could act as a surrogate, compensating for the lack of dystrophin, and, as such, it could be used in combination with dystrophin restoration therapies. Different strategies to overexpress utrophin are currently under investigation. In recent years, many compounds have been reported to modulate utrophin expression efficiently in preclinical studies and ameliorate the dystrophic phenotype in animal models of the disease. In this manuscript, we discuss the current knowledge on utrophin protein and the different mechanisms that modulate its expression in skeletal muscle. We also include a comprehensive review of compounds proposed as utrophin regulators and, as such, potential therapeutic candidates for these muscular dystrophies. | es_ES |
dc.description.sponsorship | This work was supported by funding from Health Institute Carlos III (ISCIII, Spain) and the European Regional Development Fund, (ERDF/FEDER), `A way of making Europe': Grant PI15/00333; Basque Government (grants 2016111029, 2018222035 and 2020333012) and Duchenne Parent Project Spain (grant 05/2016). P. S--M holds a Rio Hortega Fellowship from ISCIII (CM19/00104). V.A--G holds a Miguel Servet Fellowship from the ISCIII (CPII17/00004), part-funded by ERDF/FEDER. A. L--M acknowledges funding by Biocruces Bizkaia Health Research Institute (BC/I/DIV/19/001). V. A--G also acknowledges funding from Ikerbasque (Basque Foundation for Science). None of this funding represents a conflict of interest with the content of this review. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.subject | Becker muscular dystrophy | es_ES |
dc.subject | biglycan | es_ES |
dc.subject | Duchenne muscular dystrophy | es_ES |
dc.subject | dystrophin | es_ES |
dc.subject | ezutromid | es_ES |
dc.subject | therapy | es_ES |
dc.subject | utrophin | es_ES |
dc.subject | MDX mouse model | es_ES |
dc.subject | skeletal-muscleup-regulation | es_ES |
dc.subject | glycoprotein complex | es_ES |
dc.subject | gene-therapy | es_ES |
dc.subject | neuromuscular-junction | es_ES |
dc.subject | transcription factor | es_ES |
dc.subject | galnac transferase | es_ES |
dc.subject | a-utrophin | es_ES |
dc.subject | expression | es_ES |
dc.title | Utrophin modulator drugs as potential therapies for Duchenne and Becker muscular dystrophies | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.© 2021 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society | es_ES |
dc.rights.holder | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.relation.publisherversion | https://onlinelibrary.wiley.com/doi/10.1111/nan.12735 | es_ES |
dc.identifier.doi | 10.1111/nan.12735 | |
dc.departamentoes | Pediatría | es_ES |
dc.departamentoeu | Pediatria | es_ES |
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Except where otherwise noted, this item's license is described as This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.© 2021 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society