c-Abl tyrosine kinase modulates tau pathology and Cdk5 phosphorylation in AD transgenic mice

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dc.catalogadorjlo
dc.contributor.authorCancino Lobos, Gonzalo
dc.contributor.authorPérez De Arce Guzmán, Karen Andrea
dc.contributor.authorCastro Uribe, Paula Andrea
dc.contributor.authorToledo Maldonado, Enrique Daniel
dc.contributor.authorVon Bernhardi Montgomery, Rommy Edth B.
dc.contributor.authorÁlvarez Rojas, Alejandra Beatriz
dc.date.accessioned2024-04-08T16:28:47Z
dc.date.available2024-04-08T16:28:47Z
dc.date.issued2011
dc.description.abstractThe c-Abl tyrosine kinase is an important link in signal transduction pathways that promote cytoskeletal rearrangement and apoptotic signalling. We have previously shown that amyloid-beta-peptide (A beta) activates c-Abl. Herein we show that c-Abl participates in A beta-induced tau phosphorylation through Cdk5 activation. We found that intraperitoneal administration of STI571, a specific inhibitor for c-Abl kinase, decreased tau phosphorylation in the APPswe/PSEN1 Delta E9 transgenic mouse brain. In addition, when neurons were treated with A beta we observed: (i) an increase in active c-Abl and tau phosphorylation, (ii) the prevention of tau phosphorylation by STI571 and (iii) the inhibition of c-Abl expression by shRNA, as well as the expression of a c-Abl kinase death mutant, decreased AT8 and PHF1 signals. Furthermore, the increase of c-Abl was associated with Tyr15 phosphorylation of Cdk5 and its association with c-Abl. Brains from APPswe/PSEN1 Delta E9 mice showed higher levels of c-Abl and phospho-Cdk5 than wild-type mice. Moreover, STI571 treatment decreased the phospho-Cdk5 levels. Together, the evidence suggests that activation of c-Abl by A beta promotes tau phosphorylation through Tyr15 phosphorylation-mediated Cdk5 activation. (C) 2009 Elsevier Inc. All rights reserved.
dc.description.funderFONDECYT
dc.format.extent13 páginas
dc.fuente.origenHistorial Académico
dc.identifier.citationCancino, Gonzalo, Perez de Arce, Karen, Castro U, Paula, Toledo M, Enrique, Von Benhardi, Rommy, Alvarez, Alejandra. c-Abl tyrosine kinase modulates tau pathology and Cdk5 phosphorylation in AD transgenic mice . Neurobiology Of Aging. 2009;xx(xx):x-x.
dc.identifier.doi10.1016/j.neurobiolaging.2009.07.007
dc.identifier.issn0197-4580
dc.identifier.urihttp://dx.doi.org/10.1016/j.neurobiolaging.2009.07.007
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/84976
dc.identifier.wosidWOS:000292244900011
dc.information.autorucFacultad de Ciencias Biológicas; Cancino Lobos, Gonzalo; 0000-0001-8697-7282; 17709
dc.information.autorucFacultad de Ciencias Biológicas; Pérez De Arce Guzmán, Karen Andrea; S/I; 18209
dc.information.autorucFacultad de Ciencias Biológicas; Castro Uribe, Paula Andrea; S/I; 11717
dc.information.autorucFacultad de Ciencias Biológicas; Toledo Maldonado, Enrique Daniel; S/I; 4625
dc.information.autorucFacultad de Ciencias Biológicas; Von Bernhardi Montgomery, Rommy Edth B.; 0000-0002-9022-7676; 62523
dc.information.autorucFacultad de Ciencias Biológicas; Álvarez Rojas, Alejandra Beatriz; 0000-0002-8129-9280; 83681
dc.issue.numero7
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final1261
dc.pagina.inicio1249
dc.revistaNeurobiology of Aging
dc.rightsacceso restringido
dc.subjectc-Abl
dc.subjectCdk5
dc.subjectNeurotoxicity
dc.subjectTau phosphorylation
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 modulates tau pathology and Cdk5 phosphorylation in AD transgenic mice
dc.typeartículo
dc.volumen32
sipa.codpersvinculados17709
sipa.codpersvinculados18209
sipa.codpersvinculados11717
sipa.codpersvinculados4625
sipa.codpersvinculados62523
sipa.codpersvinculados83681
sipa.trazabilidadHistorial Académico;09-07-2021
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