| First Author | Wang L | Year | 2015 |
| Journal | Mol Neurodegener | Volume | 10 |
| Pages | 33 | PubMed ID | 26227811 |
| Mgi Jnum | J:326580 | Mgi Id | MGI:6862872 |
| Doi | 10.1186/s13024-015-0030-y | Citation | Wang L, et al. (2015) Conditional inactivation of Akt three isoforms causes tau hyperphosphorylation in the brain. Mol Neurodegener 10:33 |
| abstractText | BACKGROUND: Tau hyperphosphorylation plays a critical role in neurodegenerative diseases [EMBO Mol Med. 6:1142-60, 2014; Annu Rev Neurosci. 24:1121-59, 2001]. Recent evidence has shown that Akt is down-regulated in AD [J Pathol. 225:54-62, 2011]. However, it remained unknown which pathological process, e.g. tau pathology or neuron death, Akt may contribute to. In this study, Cre-loxP technique was employed to generate a viable Akt three isoforms conditional knockout (Akt cTKO) mouse in which total Akt levels were dramatically reduced in the adult brain. RESULTS: Significantly increased levels of tau phosphorylated (p-tau) at various sites were observed in Akt cTKO mice as compared to age-matched littermate controls. Increased levels for phosphorylated GSK3alpha and phosphorylated PKA substrates were detected in Akt cTKO brains. In contrast, no significant changes on p-tau levels were found in Akt1(-/-), Akt2(-/-) or Akt3(-/-) mice. CONCLUSIONS: Akt may regulate tau phosphorylation in the adult brain by affecting activities for PKA and GSK3alpha. |
