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A Drosophila model of GDAP1 function reveals the involvement of insulin signalling in the mitochondria-dependent neuromuscular degeneration

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A Drosophila model of GDAP1 function reveals the involvement of insulin signalling in the mitochondria-dependent neuromuscular degeneration

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dc.contributor.author Lopez del Amo, V es_ES
dc.contributor.author Palomino-Schätzlein, Martina es_ES
dc.contributor.author Seco-Cervera, Marta es_ES
dc.contributor.author Garcia-Gimenez, José Luis es_ES
dc.contributor.author Pallardó-Calatayud, Federico V. es_ES
dc.contributor.author Pineda-Lucena, Antonio es_ES
dc.contributor.author Galindo-Orozco, Máximo Ibo es_ES
dc.date.accessioned 2020-04-06T08:55:47Z
dc.date.available 2020-04-06T08:55:47Z
dc.date.issued 2017 es_ES
dc.identifier.issn 0925-4439 es_ES
dc.identifier.uri http://hdl.handle.net/10251/140189
dc.description.abstract [EN] Charcot-Marie-Tooth disease is a rare peripheral neuropathy for which there is no specific treatment. Some forms of Charcot-Marie-Tooth are due to mutations in the GDAP1 gene. A striking feature of mutations in GDAP1 is that they have a variable clinical manifestation, according to disease onset and progression, histology and mode of inheritance. Studies in cellular and animal models have revealed a role of GDAP1 in mitochondrial morphology and distribution, calcium homeostasis and oxidative stress. To get a better understanding of the disease mechanism we have generated models of over-expression and RNA interference of the Drosophila Gdapl gene. In order to get an overview about the changes that Gdapl mutations cause in our disease model, we have combined a comprehensive determination of the metabolic profile in the flies by nuclear magnetic resonance spectroscopy with gene expression analyses and biophysical tests. Our results revealed that both up- and down-regulation of Gdapl results in an early systemic inactivation of the insulin pathway before the onset of neuromuscular degeneration, followed by an accumulation of carbohydrates and an increase in the (3-oxidation of lipids. Our findings are in line with emerging reports of energy metabolism impairments linked to different types of neural pathologies caused by defective mitochondrial function, which is not surprising given the central role of mitochondria in the control of energy metabolism. The relationship of mitochondrial dynamics with metabolism during neurodegeneration opens new avenues to understand the cause of the disease, and for the discovery of new biomarkers and treatments. es_ES
dc.description.sponsorship This work was supported by a project grant from the Association Francaise contre les Myopathies [AFM 18540 to M.I.G]; a collaborative grant from International Rare Diseases Research consortium (IRDiRC) and Institute de Salud Carlos III [IR11/TREAT-CMT to M.I.G. (partner 12) and F.V.P. (partner 8)]; funding from Institute de Salud Carlos III through Biomedical Network Research Center for Rare Diseases and the INGENIO 2010 program to F.V.P.; and a project grant from the Spanish Government (Secretaria de Estado de Investigacion, Desarollo e Innovacion, Ministerio de Economia y Competitividad) [SAF2014-53977-R to A.P.]. es_ES
dc.language Inglés es_ES
dc.publisher Elsevier es_ES
dc.relation ISCIII/IR11/TREAT-CMT es_ES
dc.relation info:eu-repo/grantAgreement/MINECO//SAF2014-53977-R/ES/HERRAMIENTAS DE RMN PARA EL DESARROLLO DE UNA PLATAFORMA PARA LA IDENTIFIC. DE DIANAS, LA EVAL. DE FARMACOS Y LA PERSONAL. DE TRATAMIENTOS BASADA EN APROX. METABOLOMICAS/ es_ES
dc.relation Association Française contre les Myopathies/AFM 18540 es_ES
dc.relation IRDiRC/IR11/TREAT-CMT es_ES
dc.relation.ispartof Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease es_ES
dc.rights Reserva de todos los derechos es_ES
dc.subject GDAP1 es_ES
dc.subject Charcot-Marie-Tooth es_ES
dc.subject Mitochondria es_ES
dc.subject Insulin es_ES
dc.subject.classification BIOQUIMICA Y BIOLOGIA MOLECULAR es_ES
dc.title A Drosophila model of GDAP1 function reveals the involvement of insulin signalling in the mitochondria-dependent neuromuscular degeneration es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.1016/j.bbadis.2017.01.003 es_ES
dc.rights.accessRights Abierto es_ES
dc.contributor.affiliation Universitat Politècnica de València. Departamento de Biotecnología - Departament de Biotecnologia es_ES
dc.description.bibliographicCitation Lopez Del Amo, V.; Palomino-Schätzlein, M.; Seco-Cervera, M.; Garcia-Gimenez, JL.; Pallardó-Calatayud, FV.; Pineda-Lucena, A.; Galindo-Orozco, MI. (2017). A Drosophila model of GDAP1 function reveals the involvement of insulin signalling in the mitochondria-dependent neuromuscular degeneration. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1863(3):801-809. https://doi.org/10.1016/j.bbadis.2017.01.003 es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion https://doi.org/10.1016/j.bbadis.2017.01.003 es_ES
dc.description.upvformatpinicio 801 es_ES
dc.description.upvformatpfin 809 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 1863 es_ES
dc.description.issue 3 es_ES
dc.relation.pasarela S\326985 es_ES
dc.contributor.funder Instituto de Salud Carlos III es_ES
dc.contributor.funder Ministerio de Ciencia e Innovación es_ES
dc.contributor.funder Ministerio de Economía y Competitividad es_ES
dc.contributor.funder Association Française contre les Myopathies es_ES
dc.contributor.funder International Rare Diseases Research Consortium es_ES
dc.contributor.funder Centro de Investigación Biomédica en Red de Enfermedades Raras es_ES


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