Phosphorylated tau potentiates Aβ-induced mitochondrial damage in mature neurons
MetadataShow full item record
von Bernhardi R.
Tau 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.
Showing items related by title, author, creator and subject.
Truncated Tau Induces Mitochondrial Transport Failure Through the Impairment of TRAK2 Protein and Bioenergetics Decline in Neuronal Cells (2020) Quintanilla R.A.; Tapia-Monsalves C.; Vergara E.H.; Pérez M.J.; Aranguiz A. (Frontiers Media S.A., 2020)
ArticlePérez M.J.; Vergara-Pulgar K.; Jara C.; Cabezas-Opazo F.; Quintanilla R.A. (Humana Press Inc., 2018)
Quercetin Exerts Differential Neuroprotective Effects Against H2O2 and Aβ Aggregates in Hippocampal Neurons: the Role of Mitochondria (2020) Godoy J.A.; Lindsay C.B.; Quintanilla R.A.; Carvajal F.J.; Cerpa W.; Inestrosa N.C. (Humana Press Inc., 2017)