Mutations in clock proteins may be responsible for night owl effect seen in delayed sleep phase syndrome, finds study

Experts suggest that any genetic changes in clock proteins CLOCK, BMAL-1, cryptochrome, and period may disrupt our internal clock and lead to sleep phase disorder

Myupchar October 28, 2020 23:47:46 IST
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Mutations in clock proteins may be responsible for night owl effect seen in delayed sleep phase syndrome, finds study

Representational image.

Delayed sleep phase syndrome (DSPS) is a condition in which the normal sleep time of a person is delayed by about two hours beyond conventional bedtime.

Changes in the internal clock during puberty, health conditions like depression, obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD), and poor sleeping habits are considered to be some of the possible causes of DSPS. It may also be hereditary. Several studies indicate the mutations in clock proteins are responsible for DSPS.

Now, a group of researchers at the University of California San Diego say that they have found the molecular mechanism associated with the mutations in clock protein and hence DSPS.

The findings of the study are published in the peer-reviewed journal Proceedings of the National Academy of Sciences.

Clock proteins

Clock proteins are responsible for maintaining our daily cycles, also known as circadian rhythms. There are four main clock proteins, whose function is controlled by a feedback loop. Two clock proteins called CLOCK and BMAL-1 switch on the genes responsible for the production of the other two proteins called cryptochrome and period. The latter two, in turn, suppress the production of the first two proteins, controlling their own overproduction.

Experts suggest that any genetic changes in these proteins disrupt our internal clock and lead to sleep phase disorder. If the clock cycle shortens, it causes the person to go to sleep early at night and wake up early in the morning, also called the morning lack effect. If the clock cycle lengthens, the person tends to go to bed and wake up late, also called the night owl effect.

Normally, these changes are rare. However, in 2017, researchers found one genetic variant of the clock protein that was found in one in every 75 people of European descent. This is what the latest study is based on.

The mutation was found to affect one of the four main clock proteins, cryptochrome. Specifically, it occurs in the tail part of the protein, snipping the part off.

The latest study

Now, the researchers at UC San Diego have found that this snipped part of the cryptochrome protein actually helps it control the 24-hour cycle. In the absence of the tail, cryptochrome binds more tightly to the CLOCK-BMAL-1 complex and leads to the night owl effect.

This missing tail usually binds with a pocket in the protein complex. While binding, the tail competes with the binding of the rest of the complex.

In a news release by the University, the study authors explained that the tighter the complex binds to the pocket, the faster the clock runs. So, any drug that can bind to this pocket can help improve the sleep cycle in those with DSPS.

Explaining the importance of the study’s findings, Dr Carrie Partch, the corresponding author of the study, said in a news release, “We know now that we need to target that pocket to develop therapeutics that could shorten the clock for people with delayed sleep phase disorder.”

For more information, read our article on Sleep disorders

Health articles in Firstpost are written by myUpchar.com, India’s first and biggest resource for verified medical information. At myUpchar, researchers and journalists work with doctors to bring you information on all things health.

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