| First Author | Hamilton A | Year | 2014 |
| Journal | Mol Brain | Volume | 7 |
| Pages | 40 | PubMed ID | 24886239 |
| Mgi Jnum | J:316460 | Mgi Id | MGI:6837393 |
| Doi | 10.1186/1756-6606-7-40 | Citation | Hamilton A, et al. (2014) Metabotropic glutamate receptor 5 knockout reduces cognitive impairment and pathogenesis in a mouse model of Alzheimer's disease. Mol Brain 7:40 |
| abstractText | BACKGROUND: Alzheimer's disease (AD) pathology occurs in part as the result of excessive production of beta-amyloid (Abeta). Metabotropic glutamate receptor 5 (mGluR5) is now considered a receptor for Abeta and consequently contributes to pathogenic Abeta signaling in AD. RESULTS: Genetic deletion of mGluR5 rescues the spatial learning deficits observed in APPswe/PS1DeltaE9 AD mice. Moreover, both Abeta oligomer formation and Abeta plaque number are reduced in APPswe/PS1DeltaE9 mice lacking mGluR5 expression. In addition to the observed increase in Abeta oligomers and plaques in APPswe/PS1DeltaE9 mice, we found that both mTOR phosphorylation and fragile X mental retardation protein (FMRP) expression were increased in these mice. Genetic deletion of mGluR5 reduced Abeta oligomers, plaques, mTOR phosphorylation and FMRP expression in APPswe/PS1DeltaE9 mice. CONCLUSIONS: Thus, we propose that Abeta activation of mGluR5 appears to initiate a positive feedback loop resulting in increased Abeta formation and AD pathology in APPswe/PS1DeltaE9 mice via mechanism that is regulated by FMRP. |
