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dc.contributor.authorEsteban-Martos, Alvaro
dc.contributor.authorBrokate-Llanos, Ana María
dc.contributor.authorReal-Navarrete, Luis Miguel 
dc.contributor.authorMelgar-Locatelli, Sonia
dc.contributor.authorDe Rojas, Itziar
dc.contributor.authorCastro-Zavala, Adriana
dc.contributor.authorBravo-Romero, María José 
dc.contributor.authorMañas-Padilla, María del Carmen
dc.contributor.authorGarcía-González, Pablo
dc.contributor.authorRuiz-Galdón, Maximiliano 
dc.contributor.authorPacheco-Sánchez, Beatriz
dc.contributor.authorPolvillo, Rocío
dc.contributor.authorRodriguez-de-Fonseca, Fernando
dc.contributor.authorGonzález, Irene
dc.contributor.authorCastilla-Ortega, María Estela 
dc.contributor.authorMuñoz-Gómez, Manuel 
dc.contributor.authorRivera, Patricia
dc.contributor.authorReyes-Engel, Armando 
dc.contributor.authorRuiz, Agustín
dc.contributor.authorRoyo-Sánchez-Palencia, José Luis 
dc.date.accessioned2024-01-16T09:13:11Z
dc.date.available2024-01-16T09:13:11Z
dc.date.issued2023
dc.identifier.citationEsteban-Martos, A., Brokate-Llanos, A. M., Real, L. M., Melgar-Locatelli, S., de Rojas, I., Castro-Zavala, A., ... & Royo, J. L. (2023). A Functional Pipeline of Genome-Wide Association Data Leads to Midostaurin as a Repurposed Drug for Alzheimer’s Disease. International Journal of Molecular Sciences, 24(15), 12079.es_ES
dc.identifier.urihttps://hdl.handle.net/10630/28761
dc.description.abstractGenome-wide association studies (GWAS) constitute a powerful tool to identify the different biochemical pathways associated with disease. This knowledge can be used to prioritize drugs targeting these routes, paving the road to clinical application. Here, we describe DAGGER (Drug Repositioning by Analysis of GWAS and Gene Expression in R), a straightforward pipeline to find currently approved drugs with repurposing potential. As a proof of concept, we analyzed a meta-GWAS of 1.6 × 107 single-nucleotide polymorphisms performed on Alzheimer’s disease (AD). Our pipeline uses the Genotype-Tissue Expression (GTEx) and Drug Gene Interaction (DGI) databases for a rational prioritization of 22 druggable targets. Next, we performed a two-stage in vivo functional assay. We used a C. elegans humanized model over-expressing the Aβ1-42 peptide. We assayed the five top-scoring candidate drugs, finding midostaurin, a multitarget protein kinase inhibitor, to be a protective drug. Next, 3xTg AD transgenic mice were used for a final evaluation of midostaurin’s effect. Behavioral testing after three weeks of 20 mg/kg intraperitoneal treatment revealed a significant improvement in behavior, including locomotion, anxiety-like behavior, and new-place recognition. Altogether, we consider that our pipeline might be a useful tool for drug repurposing in complex diseases.es_ES
dc.description.sponsorshipDepartment of Surgery, Biochemistry and Immunology, School of Medicine, University of Malaga, Boulevard Louis Pasteur s/n, 29071 Malaga, Spain Departamento de Biología Molecular e Ingeniería Bioquímica, Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide (UPO), UPO/CSIC/JA, Ctra Utrera Km1, 41013 Sevilla, Spain Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), 28029 Madrid, Spain Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29590 Malaga, Spain Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, 29071 Malaga, Spain Research Center and Memory Clinic, Ace Alzheimer Center Barcelona—Universitat Internacional de Catalunya, 08017 Barcelona, Spain Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), National Institute of Health Carlos III, 28029 Madrid, Spain Unidad de Gestion Clinica de Salud Mental, Hospital Universitario Regional de Malaga, 29010 Malaga, Spain Funding for open Access charge: Universidad de Málaga / CBUAes_ES
dc.language.isoenges_ES
dc.publisherMDPIes_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.subject.otherAlzheimer’s diseasees_ES
dc.subject.otherGWASes_ES
dc.subject.otherMidostaurines_ES
dc.subject.otherDrug discoveryes_ES
dc.subject.otherPipelinees_ES
dc.titleA Functional Pipeline of Genome-Wide Association Data Leads to Midostaurin as a Repurposed Drug for Alzheimer’s Diseasees_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.centroFacultad de Psicología y Logopediaes_ES
dc.identifier.doi10.3390/ijms241512079
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersiones_ES


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