Enzyme may be target for new anti-inflammatory compounds

Findings may help in development of new anti-inflammatory compounds

Virginia Commonwealth University researchers studying the enzyme that triggers inflammation have found that it may be a target for a new class of anti-inflammatory drugs to treat arthritis, asthma, multiple sclerosis, lung and colon cancers and Alzheimer’s disease.

In the December issue of the Journal of Lipid Research, researchers examined the structural make-up of ceramide which is a target molecule for the enzyme known as ceramide kinase (CERK). CERK is able to recognize ceramide based on its structure. The interaction of CERK and ceramide is like a lock and key. They found that even a slight change in the structure of ceramide can significantly decrease CERK’s ability to identify its target and catalyze the reaction.

“Our findings suggest that CERK could be a novel target for a new generation of anti-inflammatory/anti-trauma therapeutics, and lay the groundwork for a rationale design of inhibitors for CERK,” said lead author Charles E. Chalfant, Ph.D., assistant professor of biochemistry at VCU.

According to Chalfant, CERK is responsible for catalyzing the process in mammals called phosphorylation that produces a signaling lipid called ceramide-1-phosphate (C1P). C1P is an important biological mediator that induces inflammatory pathways such as those blocked by many allergy medications.

“The inhibition of CERK would have the added benefit of shutting down the entire inflammatory pathway possibly alleviating side-effects caused by the medications such as Vioxx, which was recently withdrawn from the pharmaceutical market.”

This research was supported by grants from the National Institutes of Health via the National Heart, Lung, Blood Institute.