| First Author | Tian J | Year | 2019 |
| Journal | Sci Transl Med | Volume | 11 |
| Issue | 505 | PubMed ID | 31413143 |
| Mgi Jnum | J:278681 | Mgi Id | MGI:6357764 |
| Doi | 10.1126/scitranslmed.aav6278 | Citation | Tian J, et al. (2019) Disrupted hippocampal growth hormone secretagogue receptor 1alpha interaction with dopamine receptor D1 plays a role in Alzheimer's disease. Sci Transl Med 11(505) |
| abstractText | Hippocampal lesions are a defining pathology of Alzheimer's disease (AD). However, the molecular mechanisms that underlie hippocampal synaptic injury in AD have not been fully elucidated. Current therapeutic efforts for AD treatment are not effective in correcting hippocampal synaptic deficits. Growth hormone secretagogue receptor 1alpha (GHSR1alpha) is critical for hippocampal synaptic physiology. Here, we report that GHSR1alpha interaction with beta-amyloid (Abeta) suppresses GHSR1alpha activation, leading to compromised GHSR1alpha regulation of dopamine receptor D1 (DRD1) in the hippocampus from patients with AD. The simultaneous application of the selective GHSR1alpha agonist MK0677 with the selective DRD1 agonist SKF81297 rescued Ghsr1alpha function from Abeta inhibition, mitigating hippocampal synaptic injury and improving spatial memory in an AD mouse model. Our data reveal a mechanism of hippocampal vulnerability in AD and suggest that a combined activation of GHSR1alpha and DRD1 may be a promising approach for treating AD. |
