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Invisible mood switch discovered in the brain
Our brain hides a small molecular “control panel” that determines how we feel joy and how we cope with anxiety. Now, for the first time, scientists have looked inside its inner workings and found the key to creating drugs that could transform psychiatry.
The study, published in the journal Science Advances by scientists at the Icahn School of Medicine at Mount Sinai Hospital, reveals new details about the workings of the serotonin receptor 5-HT1A, a key target for antidepressants and psychedelics. This protein, embedded in the membranes of neurons, regulates the brain’s chemical signals and determines how we perceive emotions and stress.
For a long time, the receptor remained a mystery. Despite its importance, there was little data on how exactly it is activated and what molecular mechanisms influence its work. Now, using cryo-electron microscopy, a method of obtaining images with near-atomic resolution, researchers have been able to see its structure and interaction with internal signaling proteins — the so-called G proteins responsible for transmitting signals within the cell.
Scientists have found that the 5-HT1A receptor “prefers” some signaling pathways over others, regardless of the drug used. However, drugs can alter the strength of these signals. For example, the antipsychotic azapine selectively activates only one pathway, which may explain its special effects and lower risk of side effects.
An additional discovery came as a real surprise: the researchers found that a phospholipid (a fat molecule embedded in the cell membrane) acts as an auxiliary regulator of the receptor. This “co-pilot” can finely tune its activity, which has never been observed before among hundreds of similar receptors.
According to senior author Dr. Daniel Wacker, this research helps “map out” how drugs affect the receptor. This will make it possible to create more precise drugs that target specific mechanisms of depression, anxiety, or even chronic pain, reducing the risk of side effects and speeding up the onset of therapy.
In the future, the team plans to test the role of the phospholipid “cofactor” in living systems and, based on the data obtained, develop new compounds, including drugs based on psychedelic molecules. If these efforts are successful, psychiatry could move to a new level of personalized treatment, in which the impact will be directed not just at the entire brain, but at specific molecular “switches.”
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