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dc.contributor.authorQuintanilla R.A.
dc.contributor.authorvon Bernhardi R.
dc.contributor.authorGodoy J.A.
dc.contributor.authorInestrosa N.C.
dc.contributor.authorJohnson G.V.W.
dc.date.accessioned2020-09-02T22:26:29Z
dc.date.available2020-09-02T22:26:29Z
dc.date.issued2014
dc.identifier10.1016/j.nbd.2014.08.016
dc.identifier.citation71, , 260-269
dc.identifier.issn09699961
dc.identifier.urihttps://hdl.handle.net/20.500.12728/5932
dc.descriptionTau 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 Aβ 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 Aβ. 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 Aβ-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 Aβ. Interestingly, the mitochondrial failure induced by Aβ 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 Aβ-induced mitochondrial injury, which contributes to neuronal dysfunction and to the pathogenesis of AD. © 2014 Elsevier Inc.
dc.language.isoen
dc.publisherAcademic Press Inc.
dc.subjectAlzheimer's disease
dc.subjectMitochondria
dc.subjectNeuronal dysfunction
dc.subjectPHF-1
dc.subjectTau
dc.subjectamyloid precursor protein
dc.subjectgreen fluorescent protein
dc.subjectpresenilin 1
dc.subjectsuperoxide
dc.subjecttau protein
dc.subjectanimal
dc.subjectanimal embryo
dc.subjectbrain cortex
dc.subjectC57BL mouse
dc.subjectcell culture
dc.subjectchemically induced
dc.subjectcytology
dc.subjectdisorders of mitochondrial functions
dc.subjectdrug effects
dc.subjectgenetic transfection
dc.subjectgenetics
dc.subjectmetabolism
dc.subjectmitochondrial membrane potential
dc.subjectmouse
dc.subjectmutation
dc.subjectnerve cell
dc.subjectphosphorylation
dc.subjectrat
dc.subjecttransgenic mouse
dc.subjectAmyloid beta-Protein Precursor
dc.subjectAnimals
dc.subjectCells, Cultured
dc.subjectCerebral Cortex
dc.subjectEmbryo, Mammalian
dc.subjectGreen Fluorescent Proteins
dc.subjectMembrane Potential, Mitochondrial
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectMice, Transgenic
dc.subjectMitochondrial Diseases
dc.subjectMutation
dc.subjectNeurons
dc.subjectPhosphorylation
dc.subjectPresenilin-1
dc.subjectRats
dc.subjectSuperoxides
dc.subjecttau Proteins
dc.subjectTransfection
dc.titlePhosphorylated tau potentiates Aβ-induced mitochondrial damage in mature neurons
dc.typeArticle


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