| First Author | Li H | Year | 2022 |
| Journal | Commun Biol | Volume | 5 |
| Issue | 1 | Pages | 750 |
| PubMed ID | 35902736 | Mgi Jnum | J:327134 |
| Mgi Id | MGI:7327729 | Doi | 10.1038/s42003-022-03725-x |
| Citation | Li H, et al. (2022) ISX-9 potentiates CaMKIIdelta-mediated BMAL1 activation to enhance circadian amplitude. Commun Biol 5(1):750 |
| abstractText | Circadian dysregulation associates with numerous diseases including metabolic dysfunction, sleep disorder, depression and aging. Given that declined circadian amplitude is a trait commonly found with compromised health, interventions that design in precluding circadian amplitude from dampening will aid to mitigate complex, circadian-related diseases. Here we identify a neurogenic small molecule ISX-9 that is able to support persistent and higher amplitude of circadian oscillations. ISX-9 improves diurnal metabolic rhythms in middle-aged mice. Moreover, the ISX-9-treated mice show better sleep homeostasis with increased delta power during the day time and higher locomotive activity in the dark period. ISX-9 augments CaMKIIdelta expression and increases BMAL1 activity via eliciting CaMKIIdelta-mediated phosphorylation on BMAL1 residues S513/S515/S516, accordingly composes a positive feedback effect on enhancing circadian amplitude. CaMKIIdelta-targeting, and the use of ISX-9 may serve as decent choices for treating circadian-related disorders. |
