| First Author | Quintanilla RA | Year | 2014 |
| Journal | Neurobiol Dis | Volume | 71 |
| Pages | 260-9 | PubMed ID | 25134729 |
| Mgi Jnum | J:259316 | Mgi Id | MGI:6142205 |
| Doi | 10.1016/j.nbd.2014.08.016 | Citation | Quintanilla RA, et al. (2014) Phosphorylated tau potentiates Abeta-induced mitochondrial damage in mature neurons. Neurobiol Dis 71:260-9 |
| abstractText | 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 Abeta 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 Abeta. 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 Abeta-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 Abeta. Interestingly, the mitochondrial failure induced by Abeta 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 Abeta-induced mitochondrial injury, which contributes to neuronal dysfunction and to the pathogenesis of AD. |
