c-Abl tyrosine kinase down-regulation as target for memory improvement in Alzheimer's disease
dc.catalogador | dfo | |
dc.contributor.author | Leon, Rilda | |
dc.contributor.author | Gutierrez, Daniela A. | |
dc.contributor.author | Pinto, Claudio | |
dc.contributor.author | Morales Acevedo, Cristián Gonzalo | |
dc.contributor.author | de la Fuente, Catalina | |
dc.contributor.author | Riquelme, Cristobal | |
dc.contributor.author | Cortés Castro, Bastián Ignacio | |
dc.contributor.author | Gonzalez-Martin, Adrian | |
dc.contributor.author | Chamorro, David | |
dc.contributor.author | Espinosa, Nelson | |
dc.contributor.author | Fuentealba Durand, Pablo José | |
dc.contributor.author | Cancino Lobos, Gonzalo | |
dc.contributor.author | Zanlungo Matsuhiro, Silvana | |
dc.contributor.author | Dulcey, Andres E. | |
dc.contributor.author | Marugan, Juan J. | |
dc.contributor.author | Rojas, Alejandra Alvarez | |
dc.date.accessioned | 2024-04-08T20:10:26Z | |
dc.date.available | 2024-04-08T20:10:26Z | |
dc.date.issued | 2023 | |
dc.description.abstract | BackgroundGrowing 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.origen | WOS | |
dc.identifier.doi | 10.3389/fnagi.2023.1180987 | |
dc.identifier.issn | 1663-4365 | |
dc.identifier.uri | https://doi.org/10.3389/fnagi.2023.1180987 | |
dc.identifier.uri | https://repositorio.uc.cl/handle/11534/84988 | |
dc.identifier.wosid | WOS:001013034400001 | |
dc.information.autoruc | Escuela de Ingeniería; Morales Acevedo Cristian Gonzalo; S/I; 177656 | |
dc.information.autoruc | Escuela de Ingeniería; Cortes Castro Bastian Ignacio; S/I; 1087807 | |
dc.information.autoruc | Facultad de Ciencias Biológicas; Fuentealba Durand Pablo Jose; 0000-0002-9679-4612; 19184 | |
dc.information.autoruc | Facultad de Ciencias Biológicas; Cancino Lobos Gonzalo; S/I; 17709 | |
dc.information.autoruc | Facultad de Ciencias Biológicas; Zanlungo Matsuhiro Silvana; 0000-0001-8383-9829; 72650 | |
dc.language.iso | en | |
dc.nota.acceso | Contenido parcial | |
dc.pagina.final | 12 | |
dc.pagina.inicio | 1 | |
dc.revista | Frontiers in aging neuroscience | |
dc.rights | acceso abierto | |
dc.subject | c-Abl inhibitors | |
dc.subject | Tyrosine kinases | |
dc.subject | Alzheimer's disease | |
dc.subject | Memory | |
dc.subject | Hippocampi | |
dc.subject.ddc | 610 | |
dc.subject.dewey | Medicina y salud | es_ES |
dc.subject.ods | 03 Good Health and Well-being | |
dc.subject.odspa | 03 Salud y bienestar | |
dc.title | c-Abl tyrosine kinase down-regulation as target for memory improvement in Alzheimer's disease | |
dc.type | artículo | |
dc.volumen | 15 | |
sipa.codpersvinculados | 177656 | |
sipa.codpersvinculados | 1087807 | |
sipa.codpersvinculados | 19184 | |
sipa.codpersvinculados | 17709 | |
sipa.codpersvinculados | 72650 | |
sipa.trazabilidad | WOS;2023-07-30 |
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