Peroxisome proliferator-activated receptor gamma is expressed in hippocampal neurons and its activation prevents beta-amyloid neurodegeneration: role of Wnt signaling

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dc.contributor.authorInestrosa, NC
dc.contributor.authorGodoy, JA
dc.contributor.authorQuintanilla, RA
dc.contributor.authorKoenig, CS
dc.contributor.authorBronfman, M
dc.date.accessioned2024-01-10T12:07:28Z
dc.date.available2024-01-10T12:07:28Z
dc.date.issued2005
dc.description.abstractThe molecular pathogenesis of Alzheimer's disease (AD) involves the participation of the amyloid-beta-peptide (Abeta), which plays a critical role in the neurodegeneration that triggers the disease. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors, which are members of the nuclear receptor family. We report here that (1) PPARgamma is present in rat hippocampal neurons in culture. (2) Activation of PPAR-gamma by troglitazone and rosiglitazone protects rat hippocampal neurons against Abeta-induced neurodegeneration, as shown by the 3-[4,5 -2yl]-2,5-diphenyltetrazolium bromide (MTT) reduction assay, immunofluorescence using an anti-heavy neurofilament antibody, and quantitative electron microscopy. (3) Hippocampal neurons treated with several PPAR-gamma agonists, including troglitazone, rosiglitazone, and ciglitazone, prevent the excitotoxic Abeta-induced rise in bulk-free Ca2+. (4) PPARgamma activation results in the modulation of Wnt signaling components, including the inhibition of glycogen synthase kinase-3beta (GSK-3beta) and an increase of the cytoplasmic and nuclear beta-catenin levels. We conclude that the activation of PPARgamma prevents Abeta-induced neurodegeneration by a mechanism that may involve a cross talk between neuronal PPAR-y and the Writ signaling pathway. More important, the fact that the activation of PPAR-y attenuated Abeta-dependent neurodegeneration opens the possibility to fight AD from a new therapeutic perspective. (C) 2004 Published by Elsevier Inc.
dc.fechaingreso.objetodigital16-04-2024
dc.format.extent14 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.yexcr.2004.09.032
dc.identifier.eissn1090-2422
dc.identifier.issn0014-4827
dc.identifier.pubmedidMEDLINE:15707577
dc.identifier.urihttps://doi.org/10.1016/j.yexcr.2004.09.032
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/76288
dc.identifier.wosidWOS:000227127900009
dc.information.autorucCiencias Biológicas;Bronfman M;S/I;98819
dc.information.autorucCiencias Biológicas;Inestrosa N;S/I;99331
dc.information.autorucCiencias Biológicas;Konig C;S/I;48645
dc.issue.numero1
dc.language.isoen
dc.nota.accesoContenido parcial
dc.pagina.final104
dc.pagina.inicio91
dc.publisherELSEVIER INC
dc.revistaEXPERIMENTAL CELL RESEARCH
dc.rightsacceso restringido
dc.subjectAlzheimer's disease
dc.subjectA beta peptide
dc.subjectPPAR gamma
dc.subjectanti-diabetic drugs
dc.subjectcell survival
dc.subjectWnt signaling
dc.subjectGLYCOGEN-SYNTHASE KINASE-3-BETA
dc.subjectATP CHANNEL ACTIVITY
dc.subjectALZHEIMERS-DISEASE
dc.subjectPPAR-GAMMA
dc.subjectINSULIN-RESISTANCE
dc.subjectDIABETES-MELLITUS
dc.subjectKINASE
dc.subjectTROGLITAZONE
dc.subjectINHIBITION
dc.subjectDIFFERENTIATION
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titlePeroxisome proliferator-activated receptor gamma is expressed in hippocampal neurons and its activation prevents beta-amyloid neurodegeneration: role of Wnt signaling
dc.typeartículo
dc.volumen304
sipa.codpersvinculados98819
sipa.codpersvinculados99331
sipa.codpersvinculados48645
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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