Phosphorylated tau potentiates Aβ-induced mitochondrial damage in mature neurons

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dc.contributor.authorQuintanilla, Rodrigo A.
dc.contributor.authorvon Bernhardi, Rommy
dc.contributor.authorGodoy, Juan A.
dc.contributor.authorInestrosa, Nibaldo C.
dc.contributor.authorJohnson, Gail V. W.
dc.date.accessioned2025-01-23T21:42:08Z
dc.date.available2025-01-23T21:42:08Z
dc.date.issued2014
dc.description.abstractTau phosphorylated at the PHF-1 epitope (S396/S404) is likely involved in the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanisms by which tau phosphorylated at these sites negatively impacts neuronal functions are still under scrutiny. Previously, we showed that expression of tau truncated at D421 enhances mitochondrial dysfunction induced by A beta in cortical neurons. To extend these findings, we expressed tau pseudo-phosphorylated at S396/404 (T42EC) in mature and young cortical neurons and evaluated different aspects of mitochondrial function in response to A beta. Expression of T42EC did not induce significant changes in mitochondrial morphology, mitochondrial length, or mitochondrial transport, compared to GFP and full-length tau. However, T42EC expression enhanced A beta-induced mitochondrial membrane potential loss and increased superoxide levels compared to what was observed in mature neurons expressing full-length tau. The same effect was observed in mature neurons that expressed both pseudo-phosphorylated and truncated tau when they were treated with AS. Interestingly, the mitochondrial failure induced by A beta in mature neurons that expressed T42EC, was not observed in young neurons expressing T42EC. These novel findings suggest that phosphorylated tau (PHF-1 epitope) enhances A beta-induced mitochondrial injury, which contributes to neuronal dysfunction and to the pathogenesis of AD. (C) 2014 Elsevier Inc All rights reserved.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.nbd.2014.08.016
dc.identifier.eissn1095-953X
dc.identifier.issn0969-9961
dc.identifier.urihttps://doi.org/10.1016/j.nbd.2014.08.016
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/101654
dc.identifier.wosidWOS:000342549900025
dc.language.isoen
dc.pagina.final269
dc.pagina.inicio260
dc.revistaNeurobiology of disease
dc.rightsacceso restringido
dc.subjectTau
dc.subjectPHF-1
dc.subjectMitochondria
dc.subjectNeuronal dysfunction
dc.subjectAlzheimer's disease
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titlePhosphorylated tau potentiates Aβ-induced mitochondrial damage in mature neurons
dc.typeartículo
dc.volumen71
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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