| First Author | Park H | Year | 2023 |
| Journal | Brain Behav Immun | Volume | 115 |
| Pages | 295-307 | PubMed ID | 37884161 |
| Mgi Jnum | J:342442 | Mgi Id | MGI:7548099 |
| Doi | 10.1016/j.bbi.2023.10.021 | Citation | Park H, et al. (2023) GV1001 modulates neuroinflammation and improves memory and behavior through the activation of gonadotropin-releasing hormone receptors in a triple transgenic Alzheimer's disease mouse model. Brain Behav Immun 115:295-307 |
| abstractText | GV1001 protects neural cells from amyloid-beta (Abeta) toxicity and other stressors in in vitro studies and demonstrates clinically beneficial effects in patients with moderate to severe Alzheimer's disease (AD). Here, we investigated the protective effects and mechanism of action of GV1001 in triple transgenic AD (3xTg-AD) mice. We found that GV1001 improved memory and cognition in middle- and old-aged 3xTg-AD mice. Additionally, it reduced Abeta oligomer and phospho-tau (Ser202 and Thr205) levels in the brain, and mitigated neuroinflammation by promoting a neuroprotective microglial and astrocyte phenotype while diminishing the neurotoxic ones. In vitro, GV1001 bound to gonadotropin releasing hormone receptors (GnRHRs) with high affinity. Levels of cyclic adenosine monophosphate, a direct downstream effector of activated GnRHRs, increased after GV1001 treatment. Furthermore, inhibition of GnRHRs blocked GV1001-induced effects. Thus, GV1001 might improve cognitive and memory functions of 3xTg-AD mice by suppressing neuroinflammation and reducing Abeta oligomers levels and phospho-tau by activating GnRHRs and their downstream signaling pathways. |
