| First Author | Ma T | Year | 2010 |
| Journal | PLoS One | Volume | 5 |
| Issue | 9 | PubMed ID | 20862226 |
| Mgi Jnum | J:165117 | Mgi Id | MGI:4836296 |
| Doi | 10.1371/journal.pone.0012845 | Citation | Ma T, et al. (2010) Dysregulation of the mTOR pathway mediates impairment of synaptic plasticity in a mouse model of Alzheimer's disease. PLoS One 5(9) |
| abstractText | BACKGROUND: The mammalian target of rapamycin (mTOR) is an evolutionarily conserved Ser/Thr protein kinase that plays a pivotal role in multiple fundamental biological processes, including synaptic plasticity. We explored the relationship between the mTOR pathway and beta-amyloid (Abeta)-induced synaptic dysfunction, which is considered to be critical in the pathogenesis of Alzheimer's disease (AD). METHODOLOGY/PRINCIPAL FINDINGS: We provide evidence that inhibition of mTOR signaling correlates with impairment in synaptic plasticity in hippocampal slices from an AD mouse model and in wild-type slices exposed to exogenous Abeta1-42. Importantly, by up-regulating mTOR signaling, glycogen synthase kinase 3 (GSK3) inhibitors rescued LTP in the AD mouse model, and genetic deletion of FK506-binding protein 12 (FKBP12) prevented Abeta-induced impairment in long-term potentiation (LTP). In addition, confocal microscopy demonstrated co-localization of intraneuronal Abeta42 with mTOR. CONCLUSIONS/SIGNIFICANCE: These data support the notion that the mTOR pathway modulates Abeta-related synaptic dysfunction in AD. |
