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 ab
Contact: Franklin Hoke
The Wistar Institute