Scientists from the Oregon Health and Science University are using 3-D technology to actually view serotonin transporters in the brain. This research can lead to better treatments for anxiety, mood disorders, and depression.
Visualizing this molecular structure creates a platform for designing new, more effective small molecule therapeutics to treat depression and anxiety.
“The heavy toll that devastating illnesses like anxiety and depression have on families and communities is, in many ways, incalculable. Revealing the precise structure of the serotonin transporter holds tremendous promise for the development of life-changing drug treatments for these diseases,” said Eric Gouaux, Ph.D., senior scientist in the Vollum Institute at OHSU, National Academy of Sciences member, and Howard Hughes Medical Institute Investigator. Gouaux is an internationally recognized crystallographers in the area of neurotransmitter receptor and transporter structure.
Influencing virtually all human behaviors, serotonin regulates the activity of the central nervous system as well as processes throughout the body, from cardiovascular function to digestion, body temperature, endocrinology and reproduction. The serotonin transporter acts as a molecular pump for serotonin, recycling the neurotransmitter following neuronal signaling. Serotonin shapes neurological processes including sleep, mood, cognition, pain, hunger and aggression.
When SSRIs were first developed in the 1980s, the molecular identity of the transporter they targeted was unknown. In the 1990s, researchers realized that SSRIs had a common target — the serotonin transporter. By binding to the transporter and blocking serotonin from being taken back up by the transporter into the cell, SSRIs allow serotonin to remain outside of the cell longer than normal, potentially prolonging neuronal signaling. Though SSRIs are widely used to treat anxiety and depression, the molecular mechanism by which they block the transporter is not fully understood.
Gouaux’s lab used X-ray crystallography to capture images of the transporter. In this paper, they report that SSRIs lock the transporter in an outward-open conformation by loading in the central binding site, directly blocking serotonin binding.
The study, “X-ray structures and mechanism of the human serotonin transporter,” was authored by Gouaux; Jonathan A. Coleman, Ph.D.; and Evan M. Green, a research assistant who is now a Ph.D. student at University of California San Francisco.
Oregon Health & Science University. (2016, April 6). Researchers visualize brain’s serotonin pump, provide blueprint for new, more effective SSRIs: Revealing serotonin transporter’s molecular structure opens new era of drug treatments for depression and anxiety. ScienceDaily. Retrieved April 20, 2016 from www.sciencedaily.com/releases/2016/04/160406140336.htm
Everyone occasionally feels blue or sad. But these feelings are usually short-lived and pass within a couple of days. When you have depression, it interferes with daily life and causes pain for both you and those who care about you. Depression is a common but serious illness. Many people with a depressive illness never seek treatment. But the majority, even those with the most severe depression, can get better with treatment. Medications, psychotherapies, and other methods can effectively treat people with depression.Some types of depression tend to run in families. However, depression can occur in people without family histories of depression too. Scientists are studying certain genes that may make some people more prone to depression. Some genetics research indicates that risk for depression results from the influence of several genes acting together with environmental or other factors. In addition, trauma, loss of a loved one, a difficult relationship, or any stressful situation may trigger a depressive episode. Other depressive episodes may occur with or without an obvious trigger.This introductory course provides an overview to the various forms of depression, including signs and symptoms, co-existing conditions, causes, gender and age differences, and diagnosis and treatment options.
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