| First Author | Hwang KD | Year | 2017 |
| Journal | Mol Brain | Volume | 10 |
| Issue | 1 | Pages | 57 |
| PubMed ID | 29233183 | Mgi Jnum | J:351782 |
| Mgi Id | MGI:7666189 | Doi | 10.1186/s13041-017-0338-3 |
| Citation | Hwang KD, et al. (2017) Restoring synaptic plasticity and memory in mouse models of Alzheimer's disease by PKR inhibition. Mol Brain 10(1):57 |
| abstractText | Alzheimer's disease (AD) is a neurodegenerative disorder associated with deficits in cognition and synaptic plasticity. While accumulation of amyloid beta (Abeta) and hyper-phosphorylation of tau are parts of the etiology, AD can be caused by a large number of different genetic mutations and other unknown factors. Considering such a heterogeneous nature of AD, it would be desirable to develop treatment strategies that can improve memory irrespective of the individual causes. Reducing the phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha) was shown to enhance long-term memory and synaptic plasticity in naive mice. Moreover, hyper-phosphorylation of eIF2alpha is observed in the brains of postmortem AD patients. Therefore, regulating eIF2alpha phosphorylation can be a plausible candidate for restoring memory in AD by targeting memory-enhancing mechanism. In this study, we examined whether PKR inhibition can rescue synaptic and learning deficits in two different AD mouse models; 5XFAD transgenic and Abeta(1-42)-injected mice. We found that the acute treatment of PKR inhibitor (PKRi) can restore the deficits in long-term memory and long-term potentiation (LTP) in both mouse models without affecting the Abeta load in the hippocampus. Our results prove the principle that targeting memory enhancing mechanisms can be a valid candidate for developing AD treatment. |
