Ученые нашли способ блокировать в мозгу депрессию и стресс

Depression is not only about pessimism and badmood. This condition is accompanied by a number of symptoms, including a lack of vital energy, an unwillingness to get out of bed and start a new day, and sometimes a complete lack of desire to live. According to WHO estimates, about 3-7% of people in the world suffer from severe depression, this is about 350 million people. There are a huge number of causes of depression, including various diseases, hormonal imbalance, brain disorders and even polluted air. Recently, American scientists managed to find another cause of depression - this is an unusual receptor for brain cells, which is called GPR158. It has been linked to depression and anxiety. Scientists have managed to carefully study its structure, which, according to the researchers, will allow in the future to treat anxiety, depression and, possibly, other disorders by blocking it.

Scientists have discovered a receptor that causes anxiety and depression

Receptor that causes depression and prostate cancer

Despite the fact that science latelyhas made great strides in the treatment of depression, there are still many cases that do not respond to treatment. Scientists are now looking for a variety of ways to solve this problem. Not so long ago, I said that one woman with depression who did not respond to treatment even had an electrostimulator inserted into her head to stimulate certain parts of the brain when needed. However, the use of implants is a rather radical method of therapy.

Scientists from the Medical Research CenterScripps Research decided to take a different approach - they began to study receptors associated with depression. In a 2018 study, scientists were able to find that a high concentration of the GPR158 receptor is found in the prefrontal cortex of people who had a serious depressive disorder at the time of death.

Depressed mice have a high concentration of the GPR158 receptor

In addition, scientists have found that mice withchronic stress increased the level of this receptor in the prefrontal cortex, which ultimately led to depressive behavior. Then the scientists suppressed the activity of GPR158 in rodents, and found an increase in resistance to stress and depression. Moreover, the scientists also found that the activity of the GPR158 receptor is also associated with prostate cancer.

GPR158 is commonly referred to as the "orphan receptor"since scientists have not yet identified the molecule responsible for turning on its signaling function. And the receptor is also considered unusual for the reason that in the brain, unlike most receptors in its family, it exists in close connection with a protein complex called the RGS signaling complex (stands for the regulator of G protein signaling). It acts as a powerful inhibitor of cellular signaling. However, scientists were unclear why GPR158 would use it.

Treatment of depression at the biomolecular level

In his new study, the results of whichwere published November 18 in the journal Science, the researchers used cryogenic electron microscopy for the first time with a resolution of about one-third of a billionth of a meter. This allowed the creation of a detailed map of the atomic structure of the GPR158 receptor itself, as well as associated with a group of proteins that are responsible for its activity.

Scientists plan to treat depression by blocking the GPR158 receptor

“We have studied this receptor for over 10 years and for manystudied its biological research, so I am really pleased to see how it works for the first time, ”says lead author Kirill Martemyanov, Ph.D., professor and head of the Department of Neurology at Scripps Research.

As scientists note, the study of the structure of the receptorgave a lot of insight into how it works. According to the researchers, the receptor uses RGS proteins as a means of transmitting its signal. Among other unusual features, a module at the end, called a cache domain, that extends outside the cell was found. The authors believe that the cache domain serves as a trap for molecules that activate GPR158. Cache domains have never been observed in receptors of this type before, demonstrating its unique biology.

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Now the authors of the work are faced with a new task,which is to use the information obtained to develop low molecular weight therapeutic agents for the treatment of depression. At the moment, scientists are working on several possible approaches that will block the receptor - this is the destruction of its two-component structure, interfering with the operation of the RGS complex, or affecting the cache domain using small molecular binders. Further research will show which one is more effective.