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Gene-Regulating Enzyme is Also a Target for Anti-Depressive Drugs

In 2005, professor Ramin Shiekhattar, Ph.D., at The Wistar Institute and his colleagues reported details about an enzyme involved in appropriately repressing sets of neuronal genes in non-neuronal cells.

At the time, the scientists noted that the enzyme appeared to fit into the same extended enzyme family that includes monoamine oxidases, psychoactive enzymes that oxidize dopamine and norepinephrin.

Inhibitors of these enzymes have long been used to treat depression, certain other psychiatric and emotional disorders, and Parkinson’s disease.

Now, in a study published online today in the June 26 issue of Chemistry & Biology, Shiekhattar and his team show that the enzyme is itself a target for certain monoamine oxidase inhibitors used to treat depression. One member of this family of drugs in particular, called tranylcypromine (brand name Parnate®, manufactured by GlaxoSmithKline), was seen to inhibit the enzyme most strongly. The findings suggest that these anti-depressive drugs may have additional applications in other medically relevant areas.

For example, Shiekhattar notes that the enzyme studied exists in a complex with another type of gene-regulating enzyme that has been implicated in the development of cancer. Inhibitors of that second enzyme are currently in clinical trails as cancer therapies.

“Might particular monoamine oxidase inhibitors, currently used primarily to treat depression, have anti-cancer activity too?” Shiekhattar says. “Our findings indicate this could be the case, and we are currently screening these drugs against many different types of cancer to answer that question.”

Because the primary role of the enzyme is to repress sets of related genes, many other areas of potential influence for the monoamine oxidase inhibitors are possible too, according to Shiekhattar. At the very least, he says, the drugs will likely prove to be useful laboratory tools for answering fundamental questions about genetic expression.

The enzyme in question is called BHC110/LSD1, and it was the first human histone demethylase identified. The enzyme’s function is to remove methyl groups from small molecules called histones to modify them in ways that trigger gene repression. The second enzyme found in complex with BHC110/LSD1, acts in a similar way. Called a deacetylase, this enzyme removes acetyl groups from histones to repress gene expression.

In the body’s scheme for safely storing genes away until needed, DNA is tightly looped around the histones, kept secure by enzymes similar to the ones studied by the Wistar team until made accessible by the activity of other enzymes responsible for gene expression. Eight histones comprise a nucleosome, and long strings of nucleosomes coil in turn into chromatin, the basic material of chromosomes.

Source: The Wistar Institute

Gene-Regulating Enzyme is Also a Target for Anti-Depressive Drugs

Rick Nauert PhD

Rick Nauert, PhDDr. Rick Nauert has over 25 years experience in clinical, administrative and academic healthcare. He is currently an associate professor for Rocky Mountain University of Health Professionals doctoral program in health promotion and wellness. Dr. Nauert began his career as a clinical physical therapist and served as a regional manager for a publicly traded multidisciplinary rehabilitation agency for 12 years. He has masters degrees in health-fitness management and healthcare administration and a doctoral degree from The University of Texas at Austin focused on health care informatics, health administration, health education and health policy. His research efforts included the area of telehealth with a specialty in disease management.

APA Reference
Nauert PhD, R. (2015). Gene-Regulating Enzyme is Also a Target for Anti-Depressive Drugs. Psych Central. Retrieved on August 17, 2018, from https://psychcentral.com/news/2006/06/24/gene-regulating-enzyme-is-also-a-target-for-anti-depressive-drugs/39.html

 

Scientifically Reviewed
Last updated: 6 Oct 2015
Last reviewed: By John M. Grohol, Psy.D. on 6 Oct 2015
Published on PsychCentral.com. All rights reserved.