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Researchers identify new drug target for treating jet lag and shift work disorders
Date:8/30/2013

ck. They identified one gene and its corresponding protein product, called SIK1, that limits the body clock's ability to adjust to changes in the daily patterns of light and dark. In one particular experiment, when the researchers blocked the activity of SIK1 in laboratory mice, the mice adjusted faster to changes in the light-dark cycle that mimic a time zone change. The study proposes that the light-stimulated production of SIK1 in turn switches off the molecular pathway that feeds into the clock mechanism, thereby halting the shifting response of the biological clock.

"Our key contribution to the project was to manipulate the SIK1 protein pharmacologically, and we revealed that such blockage of the protein's activity in combination with exposure to a natural clock resetting agent, such as light, enhanced the clock shifting response," Duffield said. "For example, a one hour shift of the clock became two hours. We also showed this effect in both peripheral tissues as well as in the clock in the brain.

"It would appear that SIK1 plays a common role in our circadian clocks found throughout our body, and working as a hand-brake on our ability to shift our biorhythms and adjust to new time zones, whether these are real or artificial, such as those produced during shift work schedules."

In addition to the inconvenience of jet lag, disruptions in the circadian system, such as produced during shift work, have been linked to many diseases including diabetes, heart disease and cancer. Disturbances of the circadian clock have even been linked to mental disorders, such as schizophrenia, bipolar disease and seasonal affective disorder, also known as winter depression. It is important to note that approximately 16 percent of the U.S. and European workforces undertake some form of shift work.

"Having such a hand-break on the circadian clock systems makes sense so as to prevent excessive responses to environmental change, and that it is only in our modern 24-h
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Contact: Giles Duffield
Giles.E.Dufield.2@nd.edu
574-631-1834
University of Notre Dame
Source:Eurekalert

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