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Scientists Identify New Mechanism Regulating Body's 24-hour Clock
These new findings by researchers from the Florida campus of The Scripps Research Institute could provide a new target not only for jet lag, shift work, and sleep disturbances, but also for disorders that result from circadian rhythm disruption, including diabetes and obesity as well as some types of cancer.
"It's well known that the nuclear receptors RORa and REV-ERBa regulate expression of the gene BMAL1, which is vital to virtually every aspect of human physiology and a core component of the circadian clock," said Tom Burris, a professor in the Department of Molecular Therapeutics at Scripps Florida who led the study.
"BMAL1 functions as an obligate heterodimer (only working as a dimer with a partner) with either CLOCK or NPAS2 so it was unclear how RORa and REV-ERBa could control this complex. In this study, we show that both partners are targets. As we understand more about the relationship between these receptors and their gene targets, we can consider the possibility of modulating the body's core clock, especially as we continue to develop synthetic ligands targeting these two nuclear receptors."
Circadian rhythms are conserved across a wide variety of organisms, from Drosophila (fruit flies) to humans. In mammals, these rhythms respond to light signals and are controlled by the "master clock" in the brain. In the periphery, semi-autonomous clocks can respond to signals from the brain and from other cues including nutrient status.
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