A Molecule with a Pocket of Hope for Depression Relief


Scientists continue to chip away at the mysterious workings of our brain.

Recently, they made an interesting and potentially therapeutic discovery relevant to people with depressive symptoms.

Using a tremendously powerful X-ray machine, researchers illuminated the structure of CRF1, a protein receptor that plays a role in the triggering of depression and anxiety.

This study was done by Heptares Therapeutics using the X-ray machine at Diamond Light Source, the UK’s national particle accelerator.

The Molecule

The penetrating X-ray beams revealed the location of a crevice in the CRF1 molecule. One of the researchers called the crevice “a small binding pocket” for CRF1 antagonists, or chemicals that can render the molecule harmless. The pocket is a perfect target for future drug therapies. Scientists can create medications that will “pop” into the pocket and put a damper on the molecule’s effects.

“Now we know its shape, we can design a molecule that will lock into this crevice and block it so that CRF1 becomes inactive – ending the biochemical cascade that ends in stress,” said Dr. Fiona Marshall of Heptares Therapeutics.

How CRF1 Triggers Depression

The pituitary gland is divided into three hormone-producing lobes: the anterior, intermediate and posterior. The posterior lobe is made up of axons (nerve fibers) from the neurons of the hypothalamus. Hypothalamic hormones, when released, control pituitary hormone secretion.

CRF1 (corticotropin-releasing factor type 1) is a molecule located at the surface of cells on our pituitary gland. In answer to stress molecules released by the hypothalamus, CRF1 produces CRF, hormones involved in our response to stress. Over time, CRF hormones in our system can trigger symptoms of depression or anxiety.

Good News for Other Diseases Too

CRF1 is part of the Class B family of cell-membrane protein receptors. The Class B family includes receptors for hormones such as glucagon (related to blood sugar) and calcitonin (related to calcium and bones). Knowing the structure of CRF1 makes it possible to create new medications for all the Class B molecules, including those involved in diabetes and osteoporosis.

Sources: Independent and Popsci.com


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