The Stress Molecule: Is CFR1 the Source Of All Anxiety?

Researchers in the UK have discovered the molecular structure of a protein receptor responsible for creating feelings of stress and anxiety. The scientists, from pharmaceutical company Heptares Therapeutic, used the extremely powerful x-ray machine at the UK's Diamond Light Source particle accelerator center to obtain a 3D image of the stress molecule. Now that the molecule's structure is known, the researchers hope new medications can be designed to counteract its stress-causing effects to provide relief to patients suffering from severe anxiety and even depression.

The corticotropin-release factor 1 receptor, or CFR1, is located throughout the brain but is most commonly found in the pituitary gland, the brain's hormone hub. The molecule's main function is as a messenger to the pituitary gland, signaling for the gland to release stress hormones like cortisol and adrenaline that cause the increased heart rate, racing thoughts, and fear responses we all associate with stress and anxiety. These feelings are the body's normal reaction to stressful events, and in life-or-death situations they can be extremely helpful. But for people suffering from any of the several anxiety disorders recognized by the American Psychological Association, these feelings of life-or-death stress can crop up over the most mundane worries or tasks, or even for no reason, making everyday life a constant struggle.

There are currently several treatment methods available to people suffering from anxiety disorders, but due to the complexity of the human brain and the lack of understanding we still have of most psychological disorders, there's currently no go-to medical fix for debilitating anxiety.

However, scientists hope that the discovery of CFR1's complete molecular structure will allow them to create an innovative class of drugs designed to treat anxiety by basically switching off the CFR1 molecule. CFR1 knows when to tell the pituitary gland to release stress hormones because it receives a signal from other parts of the brain in the form of a smaller protein that fits into tiny pockets on the CFR1 structure. Basically, this smaller protein works like a key by fitting into a specially shaped "keyhole" on the CFR1 protein receptor, and when the key is inserted, CFR1 is activated and passes the message on to the brain that it's time to stress out.

The researchers' goal is to keep the key out of the keyhole by designing a synthetic molecule that is shaped almost exactly the same as the protein that acts as CFR1's "key." That way, the new molecule can fit into the receptor and keep the signal protein out, so the key never enters the ignition and CFR1 never knows to pass on its message to the pituitary gland.

This new direction of treating anxiety through deactivating the CFR1 molecule promises to be much more successful than current drugs used to treat the disorder, as it prevents excessive anxiety at the source. Research into this process could also open doors to new treatments for other medical conditions, including osteoporosis and Type 2 diabetes, since these diseases can be traced back to protein receptor molecules that are very similar in shape and function to CFR1. Although this is all still in the early stages of research and development, this new discovery is very promising for people living with severe anxiety and hopefully will lead the way to innovative new treatments.