Neuroprotective Effect of IND1316, an Indole-Based AMPK Activator, in Animal Models of Huntington Disease.
Por:
Vela M, García-Gimeno MA, Sanchis A, Bono-Yagüe J, Cumella J, Lagartera L, Pérez C, Priego EM, Campos A, Sanz P, Vázquez-Manrique RP and Castro A
Publicada:
19 ene 2022
Ahead of Print:
28 dic 2021
Resumen:
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.
Filiaciones:
Vela M:
Instituto de Química Médica, IQM-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain
García-Gimeno MA:
Department of Biotechnology, Escuela Técnica Superior de Ingeniería Agronómica y del Medio Natural (ETSIAMN), Universitat Politècnica de València, 46022 Valencia, Spain
:
Grupo de Investigación en Biomedicina Molecular, Celular y Genómica, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain
Joint Unit for Rare Diseases IIS La Fe-CIPF, 46012 Valencia, Spain
Bono-Yagüe J:
Grupo de Investigación en Biomedicina Molecular, Celular y Genómica, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain
Joint Unit for Rare Diseases IIS La Fe-CIPF, 46012 Valencia, Spain
Cumella J:
Instituto de Química Médica, IQM-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain
Lagartera L:
Instituto de Química Médica, IQM-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain
Pérez C:
Instituto de Química Médica, IQM-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain
Priego EM:
Instituto de Química Médica, IQM-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain
Campos A:
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER)-ISCIII, 28029 Madrid, Spain
Instituto de Biomedicina de Valencia, IBV-CSIC, 46010 Valencia, Spain
Sanz P:
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER)-ISCIII, 28029 Madrid, Spain
Instituto de Biomedicina de Valencia, IBV-CSIC, 46010 Valencia, Spain
:
Grupo de Investigación en Biomedicina Molecular, Celular y Genómica, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain
Joint Unit for Rare Diseases IIS La Fe-CIPF, 46012 Valencia, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER)-ISCIII, 28029 Madrid, Spain
Castro A:
Instituto de Química Médica, IQM-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain
Green Accepted
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