Can synthetic molecules conquer jet lag?

Scientists in Japan have synthesized molecules that can modify your circadian rhythm, opening the door for potential treatments for sleep disorders and disruptions caused by jet lag or shift work

Scientists have spent a lot of late nights studying the biological clocks of humans and other mammals, and have made discoveries about how our circadian rhythm works and how it could be modified. Now, researchers in Japan have synthesized molecules that can shorten our sleep cycle and potentially help with health problems caused by jet lag, shift work and sleep disorders.

Potential ways to reset the biological clock include using lasers and optical fibers to artificially stimulate the relevant area of the brain, or blocking enzymes that respond to light and dark cycles. Along similar lines, scientists at the Institute of Transformative Bio-Molecules (ITbM), at Nagoya University, have synthesized molecules that target specific proteins key to the circadian rhythm.

In basic terms, our biological clock is run by four proteins that are activated, produced, and blocked from further production in a cycle that lasts about 24 hours, dictating our need for sleep. Proteins called CLOCK and BMAL1 combine to increase production of PER and CRY proteins, and as these latter two build up, they block production of CLOCK and BMAL1, and as a result, their own production as well. As the PER and CRY proteins degrade, they eventually stop inhibiting CLOCK and BMAL1, and the cycle starts over.

Another compound, FBXL3, influences the cycle by flagging CRY for degradation, speeding up the process. The ITbM researchers focused on a molecule known as KL001, which can lengthen the cycle by competing with FBXL3, slowing its degradation of CRY. They analyzed its structure and developed compounds similar to KL001 but with the opposite effect, creating synthetic molecules that target CRY directly and shorten the cycle.

In a practical sense, a shorter rhythm means you'll feel the need to sleep sooner, and should be able to get your sleep cycle back on track quicker after an international flight or overnight shift at work.

The researchers say there's still a lot left to learn though, so don't expect a quick fix for jet lag anytime soon. Their results appeared in Asia Research News 2016 magazine.

"We hope we can make further use of synthetic chemistry to make bioactive molecules that can control the circadian rhythm of animals and gain further insight into the circadian clock mechanism, which will surely contribute to medical applications, food production and advances in clock research," says Takashi Yoshimura, one of the authors of the article.

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