This article is from WeChat official account:Academic headlines (ID: SciTouTiao), author: Caoqi Tong, from the title figure: vision China
“Being sleepy during the day and being energized at night” seems to have become the standard biological routine for more and more young people today. Chasing dramas, eating melons, games, supper… It’s early morning every time I lie down and really prepare to fall asleep.
So, this “chronic suicide” lifestyle is really just our own decision? Actually not.
(Source: Pixabay)
Recently, a recent study by researchers from the University of California, Santa Cruz and their collaborators showed that genetic mutations in the human body may also disrupt the biological clock, leading to a common sleep disorder—— Sleep phase delay disorder(delayed sleep phase disorder), it will also form the habit of “sleeping late and waking up late”. People with sleep disorders often don’t fall asleep until late at night, and of course it becomes more difficult for them to get up early.
As early as 2017, scientists discovered that a special mutation in the gene CRY1 can change the daily rhythm of the human body.A key component of the biological clock causes sleep disorders. In the latest work, the researchers are further revealing the molecular mechanism of the CRY1 gene mutation, and point out the direction for potential treatment options.
In their research work, they have revealed the molecular mechanism of gene mutations that cause sleep disorders, and pointed out the direction for potential treatment options.
Related work titled “The human CRY1 tail controls circadian timing by regulating its association with CLOCK:BMAL1” was published in the Proceedings of the National Academy of Sciences on October 26. (Proceedings of The National Academy of Sciences, PNAS).
(Source: PNAS)
One of the authors of the paper and a professor at the University of California, Carrie Parch(Carrie Partch) said, “This genetic mutation has an impact on people’s sleep The pattern has a significant impact. Therefore, finding a specific mechanism in the biological clock to link the biochemical reaction of this protein with the control of human sleep behavior is a direction worth exploring.”
This mutation is very common
For many years, Pach has been studying the molecular structure and interaction of clock proteins (clock proteins). In a study published earlier this yearHer lab has revealed how certain mutations can shorten clock time by affecting molecular switching mechanisms, which makes some people extremely fond of early wake-up mechanisms.
Almost every routine cycle of our daily physiological activities is driven by the cyclic interaction of clock proteins in the cell. The mutant protein produced by the mutant biological clock gene can change the time of the biological clock and cause sleep disorders. People with a shorter biological clock cycle are more likely to go to bed early and get up early. On the contrary, it will cause people to go to bed late.
Pach said that most of the known mutations that can alter the biological clock are very rare. For scientists, they are important clues to understanding the mechanism of the biological clock, although a specific mutation may only affect one in a million people. But unlike normal genetic mutations, the “night owl” gene seems to have a wider impact-approximately one in 75 European descendants has this genetic mutation.
He also said that it is not yet clear how much this particular mutation affects sleep disorders. Sleeping behavior is very complicated, people stay up late for many reasons, and the cause of circadian clock disorder is also difficult to determine. Therefore, the discovery of a relatively common genetic variant associated with sleep disorders is a surprising development.
“This gene mutation is really common. Although we still need to understand the role of longer biological clock time in sleep delay, this mutation is obviously an important cause of human nocturnal behavior.” Pachi Say.
How to work
This mutation affects a protein called cryptochrome (cryptochrome). Cryptochromes are a class of flavin proteins that are sensitive to blue light. They exist in plants and animals. Cryptochromes are involved in the circadian rhythm of plants and animals, and may also be involved in magnetic field sensing of many species. Although many studies have shown that the tail of cryptochrome affects the circadian rhythm, its molecular mechanism is still unclear.
Cryptochrome is one of the four main clock proteins. Among the four clock proteins, two clock proteins(CLOCK and BMAL1) form a complex and activate the other two proteins(Cyclin and Cryptochrome) gene, the latter will produce negative feedback inhibitionThe activity of a pair will weaken its activity again and return to the initial state in order to start the cycle again. This feedback loop is the central mechanism of the biological clock, driving daily fluctuations in gene activity and protein levels throughout the body.
Pach’s laboratory found that cryptochrome mutations caused a small segment of the gene to be missed in the “tail” of the transported protein. This deletion also further enhanced the combination of cryptochrome with the circadian clock BMAL1 complex The tightness of the.
“The clipped area actually controls the activity of the cryptochrome, helping to form a 24-hour biological clock. Without it, the cryptochrome will bind more tightly to the receptor protein. As a result, the cycle time is continuously extended, leading to the length of the clock every day.” Paige explained.
The protein complex produced by the combination of these cryptochromes has a gap, where the missing tail segment will compete with each other and interfere with the binding of the rest of the complex. Paige explained, “The complex structure and the tightness of the gap determine the speed of the clock.”
“This tells us that we should look for drugs that have the same effect as the cryptochrome tail.”
Currently, this is what Pachi’s laboratory is doing, conducting screening analyses to identify molecules that bind to the pockets of the clock molecule complex.
“We need to take the role of this gap as a breakthrough and develop a therapy that can shorten the clock of patients with sleep disorders.”
Reference: Scientists discover how a common mutation leads to “night owl” sleep disorder. (nd). Retrieved October 28, 2020, from
https://medicalxpress.com/news/2020-10-scientists-common-mutation-night-owl.html
This article is from WeChat official account:Academic headlines (ID: SciTouTiao) author: Caoqi Tong