Attack is not always the best defense
But the team of researchers working together with the Jena pharmacist has now developed three active agents which may be able to improve the healing of inflammatory illnesses better in future. The scientists present the potential therapeutic agents in renowned scientific journals. The agents are able to suppress a key enzyme in the body's own cascade of inflammation.
"The enzyme called 5-LOX plays a pivotal role in the synthesis of so-called leukotrienes, which are part of numerous immunological and inflammatory processes," Prof. Werz explains. Hence, the effort to prevent the synthesis of leukotrienes has been the focus of international research for inflammatory therapy for a long time. "Thousands of publications on the subject have emerged in the last 30 years," says Werz. But apart from one exception none of these efforts have made it to the stage of an approved medication. Either the efficacy of the substances was poor or they were accompanied by unwanted side effects.
As a reason behind this, the Jena pharmacist sees the insufficient understanding of cellular regulation of the leukotriene biosynthesis and the lack of knowledge of the molecular mechanisms of agent and target molecule. "Instead of testing a number of substances to see if one of them might show any activity, we took a close look at 5-LOX and tried to find where exactly this enzyme is vulnerable and what the agents, which can interact with our target molecule, should look like," Werz describes the basis-orientated approach. In this way the scientists of the
A related substance of the red-violet natural dye indirubin, called 6-BIO, proved to be similarly promising. For this substance, the Jena researchers were able to clarify the mechanism of action as well: the 6-BIO inhibits the enzyme 5-LOX by blocking receptor sites for other molecules which are necessary for it to work properly. "In addition, 6-BIO also intervenes with the synthesis of additional inflammatory factors - the cytokines implying additional synergistic effects." This is why 6-BIO could for instance be of interest for the therapy of Alzheimer's disease, in which cytokines are also playing a role.
The third possible active agent from the
Keywords for this news article include: Therapy, Eicosanoids, Leukotrienes, Enzymes and Coenzymes, Friedrich-Schiller-Universitaet Jena.
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