| First Author | Zhang C | Year | 2016 |
| Journal | Alzheimers Dement | Volume | 12 |
| Issue | 5 | Pages | 527-37 |
| PubMed ID | 26555315 | Mgi Jnum | J:351762 |
| Mgi Id | MGI:7664217 | Doi | 10.1016/j.jalz.2015.09.007 |
| Citation | Zhang C, et al. (2016) Corticotropin-releasing factor receptor-1 antagonism mitigates beta amyloid pathology and cognitive and synaptic deficits in a mouse model of Alzheimer's disease. Alzheimers Dement 12(5):527-37 |
| abstractText | INTRODUCTION: Stress and corticotropin-releasing factor (CRF) have been implicated as mechanistically involved in Alzheimer's disease (AD), but agents that impact CRF signaling have not been carefully tested for therapeutic efficacy or long-term safety in animal models. METHODS: To test whether antagonism of the type-1 corticotropin-releasing factor receptor (CRFR1) could be used as a disease-modifying treatment for AD, we used a preclinical prevention paradigm and treated 30-day-old AD transgenic mice with the small-molecule, CRFR1-selective antagonist, R121919, for 5 months, and examined AD pathologic and behavioral end points. RESULTS: R121919 significantly prevented the onset of cognitive impairment in female mice and reduced cellular and synaptic deficits and beta amyloid and C-terminal fragment-beta levels in both genders. We observed no tolerability or toxicity issues in mice treated with R121919. DISCUSSION: CRFR1 antagonism presents a viable disease-modifying therapy for AD, recommending its advancement to early-phase human safety trials. |
