The c-Abl/p73 pathway induces neurodegeneration in a Parkinson's disease model

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dc.catalogadordfo
dc.contributor.authorMarín Marín, Tamara Alejandra
dc.contributor.authorValls Jimenez, Cristián Felipe
dc.contributor.authorJerez C.
dc.contributor.authorHuerta T.
dc.contributor.authorElgueta D.
dc.contributor.authorVidal R.L.
dc.contributor.authorAlvaréz Rojas, Alejandra Beatriz
dc.contributor.authorCancino, Gonzalo
dc.date.accessioned2024-04-10T14:11:48Z
dc.date.available2024-04-10T14:11:48Z
dc.date.issued2022
dc.description.abstractParkinson's disease is the second most common neurodegenerative disorder. Although it is clear that dopaminergic neurons degenerate, the underlying molecular mechanisms are still unknown, and thus, successful treatment is still elusive. One pro-apoptotic pathway associated with several neurodegenerative diseases is the tyrosine kinase c-Abl and its target p73. Here, we evaluated the contribution of c-Abl and p73 in the degeneration of dopaminergic neurons induced by the neurotoxin 6-hydroxydopamine as a model for Parkinson's disease. First, we found that in SH-SY5Y cells treated with 6-hydroxydopamine, c-Abl and p73 phosphorylation levels were up-regulated. Also, we found that the pro-apoptotic p73 isoform TAp73 was up-regulated. Then, to evaluate whether c-Abl tyrosine kinase activity is necessary for 6-hydroxydopamine-induced apoptosis, we co-treated SH-SY5Y cells with 6-hydroxydopamine and Imatinib, a c-Abl specific inhibitor, observing that Imatinib prevented p73 phosphorylation, TAp73 up-regulation, and protected SH-SY5Y cells treated with 6-hydroxydopamine from apoptosis. Interestingly, this observation was confirmed in the c-Abl conditional null mice, where 6-hydroxydopamine stereotaxic injections induced a lesser reduction of dopaminergic neurons than in the wild-type mice significantly. Finally, we found that the intraperitoneal administration of Imatinib prevented the death of dopaminergic neurons induced by injecting 6-hydroxydopamine stereotaxically in the mice striatum. Thus, our findings support the idea that the c-Abl/p73 pathway is involved in 6-hydroxydopamine degeneration and suggest that inhibition of its kinase activity might be used as a therapeutical drug in Parkinson's disease.
dc.description.funderFONDECYT
dc.description.funderFONDEF
dc.fechaingreso.objetodigital2024-04-10
dc.fuente.origenScopus
dc.fuente.origenORCID
dc.identifier.doi10.1016/j.ibneur.2022.10.006
dc.identifier.eissn2667-2421
dc.identifier.scopusidSCOPUS_ID:85140481694
dc.identifier.urihttps://www.journals.elsevier.com/ibro-neuroscience-reports
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/85020
dc.identifier.wosidWOS:000880761700002
dc.information.autorucEscuela de Medicina; Marin Marin Tamara Alejandra; S/I; 249923
dc.information.autorucFacultad de Ciencias Biológicas; Valls Jimenez Cristian Felipe; S/I; 179040
dc.information.autorucFacultad de Ciencias Biológicas; Alvarez Rojas Alejandra Beatriz; 0000-0002-8129-9280; 83681
dc.language.isoen
dc.nota.accesoContenido completo
dc.pagina.final387
dc.pagina.inicio378
dc.revistaIBRO Neuroscience Reports
dc.rightsacceso abierto
dc.subject6-hydroxydopamine
dc.subjectc-Abl
dc.subjectNeurodegeneration
dc.subjectp73
dc.subjectParkinson's disease
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleThe c-Abl/p73 pathway induces neurodegeneration in a Parkinson's disease model
dc.typeartículo
dc.volumen13
sipa.codpersvinculados249923
sipa.codpersvinculados179040
sipa.codpersvinculados83681
sipa.trazabilidadSCOPUS;10-11-2022
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