| First Author | Hamilton A | Year | 2016 |
| Journal | Cell Rep | Volume | 15 |
| Issue | 9 | Pages | 1859-65 |
| PubMed ID | 27210751 | Mgi Jnum | J:235961 |
| Mgi Id | MGI:5804056 | Doi | 10.1016/j.celrep.2016.04.077 |
| Citation | Hamilton A, et al. (2016) Chronic Pharmacological mGluR5 Inhibition Prevents Cognitive Impairment and Reduces Pathogenesis in an Alzheimer Disease Mouse Model. Cell Rep 15(9):1859-65 |
| abstractText | Beta-amyloid (Abeta) oligomers contribute to the pathophysiology of Alzheimer disease (AD), and metabotropic glutamate receptor 5 (mGluR5) has been shown to act as a receptor for both Abeta oligomers and cellular prion proteins. Furthermore, the genetic deletion of mGluR5 in an APPswe/PS1DeltaE9 mouse model of AD improves cognitive function and reduces Abeta plaques and Abeta oligomer concentrations. Here, we show that chronic administration of the orally bioavailable mGluR5-selective negative allosteric modulator CTEP, which is similar in structure, potency, and selectivity to Basimglurant (RO4917523), which is currently in phase II clinical development for major depressive disorder and fragile X syndrome, reverses cognitive decline in APPswe/PS1DeltaE9 mice and reduces Abeta plaque deposition and soluble Abeta oligomer concentrations in both APPswe/PS1DeltaE9 and 3xTg-AD male mice. These findings suggest that CTEP or its analogue Basimglutant might potentially be an effective therapeutic for the treatment of AD patients. |
