c-Abl tyrosine kinase down-regulation as target for memory improvement in Alzheimer's disease

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dc.catalogadordfo
dc.contributor.authorLeon, Rilda
dc.contributor.authorGutierrez, Daniela A.
dc.contributor.authorPinto, Claudio
dc.contributor.authorMorales Acevedo, Cristián Gonzalo
dc.contributor.authorde la Fuente, Catalina
dc.contributor.authorRiquelme, Cristobal
dc.contributor.authorCortés Castro, Bastián Ignacio
dc.contributor.authorGonzalez-Martin, Adrian
dc.contributor.authorChamorro, David
dc.contributor.authorEspinosa, Nelson
dc.contributor.authorFuentealba Durand, Pablo José
dc.contributor.authorCancino Lobos, Gonzalo
dc.contributor.authorZanlungo Matsuhiro, Silvana
dc.contributor.authorDulcey, Andres E.
dc.contributor.authorMarugan, Juan J.
dc.contributor.authorRojas, Alejandra Alvarez
dc.date.accessioned2024-04-08T20:10:26Z
dc.date.available2024-04-08T20:10:26Z
dc.date.issued2023
dc.description.abstractBackgroundGrowing evidence suggests that the non-receptor tyrosine kinase, c-Abl, plays a significant role in the pathogenesis of Alzheimer's disease (AD). Here, we analyzed the effect of c-Abl on the cognitive performance decline of APPSwe/PSEN1 & UDelta;E9 (APP/PS1) mouse model for AD. MethodsWe used the conditional genetic ablation of c-Abl in the brain (c-Abl-KO) and pharmacological treatment with neurotinib, a novel allosteric c-Abl inhibitor with high brain penetrance, imbued in rodent's chow. ResultsWe found that APP/PS1/c-Abl-KO mice and APP/PS1 neurotinib-fed mice had improved performance in hippocampus-dependent tasks. In the object location and Barnes-maze tests, they recognized the displaced object and learned the location of the escape hole faster than APP/PS1 mice. Also, APP/PS1 neurotinib-fed mice required fewer trials to reach the learning criterion in the memory flexibility test. Accordingly, c-Abl absence and inhibition caused fewer amyloid plaques, reduced astrogliosis, and preserved neurons in the hippocampus. DiscussionOur results further validate c-Abl as a target for AD, and the neurotinib, a novel c-Abl inhibitor, as a suitable preclinical candidate for AD therapies.
dc.fuente.origenWOS
dc.identifier.doi10.3389/fnagi.2023.1180987
dc.identifier.issn1663-4365
dc.identifier.urihttps://doi.org/10.3389/fnagi.2023.1180987
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/84988
dc.identifier.wosidWOS:001013034400001
dc.information.autorucEscuela de Ingeniería; Morales Acevedo Cristian Gonzalo; S/I; 177656
dc.information.autorucEscuela de Ingeniería; Cortes Castro Bastian Ignacio; S/I; 1087807
dc.information.autorucFacultad de Ciencias Biológicas; Fuentealba Durand Pablo Jose; 0000-0002-9679-4612; 19184
dc.information.autorucFacultad de Ciencias Biológicas; Cancino Lobos Gonzalo; S/I; 17709
dc.information.autorucFacultad de Ciencias Biológicas; Zanlungo Matsuhiro Silvana; 0000-0001-8383-9829; 72650
dc.language.isoen
dc.nota.accesoContenido parcial
dc.pagina.final12
dc.pagina.inicio1
dc.revistaFrontiers in aging neuroscience
dc.rightsacceso abierto
dc.subjectc-Abl inhibitors
dc.subjectTyrosine kinases
dc.subjectAlzheimer's disease
dc.subjectMemory
dc.subjectHippocampi
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titlec-Abl tyrosine kinase down-regulation as target for memory improvement in Alzheimer's disease
dc.typeartículo
dc.volumen15
sipa.codpersvinculados177656
sipa.codpersvinculados1087807
sipa.codpersvinculados19184
sipa.codpersvinculados17709
sipa.codpersvinculados72650
sipa.trazabilidadWOS;2023-07-30
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