| First Author | Hodges SL | Year | 2018 |
| Journal | Neuroreport | Volume | 29 |
| Issue | 13 | Pages | 1109-1113 |
| PubMed ID | 29965873 | Mgi Jnum | J:324518 |
| Mgi Id | MGI:6884290 | Doi | 10.1097/WNR.0000000000001081 |
| Citation | Hodges SL, et al. (2018) Molecular interplay between hyperactive mammalian target of rapamycin signaling and Alzheimer's disease neuropathology in the NS-Pten knockout mouse model. Neuroreport 29(13):1109-1113 |
| abstractText | Dysregulation of the PI3K/Akt/mTOR signaling cascade has been associated with the pathology of neurodegenerative disorders, specifically Alzheimer's disease (AD). Both in-vivo models and post-mortem brain samples of individuals with AD have commonly shown hyperactivation of the pathway. In the present study, we examine how neuron subset-specific deletion of Pten (NS-Pten) in mice, which presents with hyperactive mammalian target of rapamycin (mTOR) activity, affects the hippocampal protein levels of key neuropathological hallmarks of AD. We found NS-Pten knockout (KO) mice to have elevated levels of amyloid-beta, alpha-synuclein, neurofilament-L, and pGSK3alpha in the hippocampal synaptosome compared with NS-Pten wild type mice. In contrast, there was a decreased expression of amyloid precursor protein, tau, GSK3alpha, and GSK3beta in NS-Pten KO hippocampi. Overall, there were significant alterations in levels of proteins associated with AD pathology in NS-Pten KO mice. This study provides novel insight into how altered mTOR signaling is linked to AD pathology, without the use of an in-vivo AD model that already displays neuropathological hallmarks of the disease. |
