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dc.contributor.author | Vela, Marta | es_ES |
dc.contributor.author | García-Gimeno, María Adelaida | es_ES |
dc.contributor.author | Sanchis, Ana | es_ES |
dc.contributor.author | Bono-Yagüe, José | es_ES |
dc.contributor.author | Cumella, José | es_ES |
dc.contributor.author | Lagartera, Laura | es_ES |
dc.contributor.author | Pérez, Concepción | es_ES |
dc.contributor.author | Priego, Eva María | es_ES |
dc.contributor.author | Campos, Angela | es_ES |
dc.contributor.author | Sanz, Pascual | es_ES |
dc.contributor.author | Vázquez-Manrique, Rafael P. | es_ES |
dc.contributor.author | Castro, Ana | es_ES |
dc.date.accessioned | 2024-02-07T19:02:41Z | |
dc.date.available | 2024-02-07T19:02:41Z | |
dc.date.issued | 2022-01-19 | es_ES |
dc.identifier.uri | http://hdl.handle.net/10251/202406 | |
dc.description.abstract | [EN] Aggregation of mutant huntingtin, because of an expanded polyglutamine track, underlies the cause of neurodegeneration in Huntington disease (HD). However, it remains unclear how some alterations at the cellular level lead to specific structural changes in HD brains. In this context, the neuroprotective effect of the activation of AMP-activated protein kinase (AMPK) appears to be a determinant factor in several neurodegenerative diseases, including HD. In the present work, we describe a series of indole-derived compounds able to activate AMPK at the cellular level. By using animal models of HD (both worms and mice), we demonstrate the in vivo efficacy of one of these compounds (IND1316), confirming that it can reduce the neuropathological symptoms of this disease. Taken together, in vivo results and in silico studies of druggability, allow us to suggest that IND1316 could be considered as a promising new lead compound for the treatment of HD and other central nervous system diseases in which the activation of AMPK results in neuroprotection. | es_ES |
dc.description.sponsorship | We thank the CGC, which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440), for providing worm strains. RPVM is a Miguel Servet type II researcher (CPII16/00004) funded by Instituto de Salud Carlos III (ISCIII, Madrid, Spain). Grants from the ISCIII (PI17/00011 and PI20/00114), the Spanish Ministerio de Ciencia Innovacion y Universidades (RTI2018-095544-B-I00) and the Fundacio Marato de TV3 (Ref.: 559) were used to perform this work . All grants from ISCIII are co-financed by the European Development Regional Fund "A way to achieve Europe" (ERDF). Funds from the Fundacion Ramon Areces were also used (CIVP19S8119). J.B.Y . holds a grant by the Generalitat Valenciana and the European Social Fund (ACIF/2019/249). R.V.M. received an Ayuda Miguel Gil grant to RPVM (VII Convocatoria Ayudas a la Investigacion MHER, 2019, cofinanced by Colegio Oficial de Farmaceuticos de Sevilla and Fundacion Cajasol). R.V.M. has also received funds from the Asociacion Valenciana de Enfermedad de Huntington (AVAEH) . This work was also supported by an intramural ACCI2016 grant from the CIBERER-ISCiii to A.C., P.S., and R.V.M. | es_ES |
dc.language | Inglés | es_ES |
dc.publisher | American Chemical Society | es_ES |
dc.relation.ispartof | ACS Chemical Neuroscience | es_ES |
dc.rights | Reserva de todos los derechos | es_ES |
dc.subject | ADME in silico | es_ES |
dc.subject | AMPK | es_ES |
dc.subject | C. elegans models | es_ES |
dc.subject | Huntington disease mouse models | es_ES |
dc.subject | Indole derivatives | es_ES |
dc.subject | Neuroprotection | es_ES |
dc.subject | PolyQ toxicity | es_ES |
dc.subject.classification | BIOQUIMICA Y BIOLOGIA MOLECULAR | es_ES |
dc.title | Neuroprotective Effect of IND1316, an Indole-Based AMPK Activator, in Animal Models of Huntington Disease | es_ES |
dc.type | Artículo | es_ES |
dc.identifier.doi | 10.1021/acschemneuro.1c00758 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-095544-B-I00/ES/ABORDAJE DE LAS ENFERMEDADES CRONICAS CON NUEVOS ENFOQUES TERAPEUTICOS PARA MODULAR EL SISTEMA ENDOCANNABINOIDE/ | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F00114/ES/MODULATING THE ACTIVITY OF GENES CONTROLLING FAT METABOLISM AS A THERAPEUTIC STRATEGY IN HUNTINGTON DISEASE/ | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/MINECO//CPII16%2F00004/ES/CPII16%2F00004/ | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/GVA//ACIF%2F2019%2F249/ | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ISCIII//PI17%2F00011/ | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/NIH//P40 OD010440/ | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/CIBERER//ACCI 2016/ | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/Fundación Ramón Areces//CIVP19S8119/ | es_ES |
dc.rights.accessRights | Abierto | es_ES |
dc.contributor.affiliation | Universitat Politècnica de València. Escuela Técnica Superior de Ingeniería Agronómica y del Medio Natural - Escola Tècnica Superior d'Enginyeria Agronòmica i del Medi Natural | es_ES |
dc.description.bibliographicCitation | Vela, M.; García-Gimeno, MA.; Sanchis, A.; Bono-Yagüe, J.; Cumella, J.; Lagartera, L.; Pérez, C.... (2022). Neuroprotective Effect of IND1316, an Indole-Based AMPK Activator, in Animal Models of Huntington Disease. ACS Chemical Neuroscience. 13(2):275-287. https://doi.org/10.1021/acschemneuro.1c00758 | es_ES |
dc.description.accrualMethod | S | es_ES |
dc.relation.publisherversion | http://doi.org/10.1021/acschemneuro.1c00758 | es_ES |
dc.description.upvformatpinicio | 275 | es_ES |
dc.description.upvformatpfin | 287 | es_ES |
dc.type.version | info:eu-repo/semantics/publishedVersion | es_ES |
dc.description.volume | 13 | es_ES |
dc.description.issue | 2 | es_ES |
dc.identifier.eissn | 1948-7193 | es_ES |
dc.identifier.pmid | 34962383 | es_ES |
dc.identifier.pmcid | PMC8822144 | es_ES |
dc.relation.pasarela | S\508408 | es_ES |
dc.contributor.funder | Fundación Cajasol | es_ES |
dc.contributor.funder | Generalitat Valenciana | es_ES |
dc.contributor.funder | Fundación Ramón Areces | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.contributor.funder | Agencia Estatal de Investigación | es_ES |
dc.contributor.funder | European Regional Development Fund | es_ES |
dc.contributor.funder | National Institutes of Health, EEUU | es_ES |
dc.contributor.funder | Ministerio de Economía y Competitividad | es_ES |
dc.contributor.funder | Colegio Oficial de Farmacéuticos de Sevilla | es_ES |
dc.contributor.funder | Asociación Valenciana de Enfermedad de Huntington | es_ES |
dc.contributor.funder | Centro de Investigación Biomédica en Red de Enfermedades Raras | es_ES |