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Unexpected new mechanism behind rheumatoid arthritis
Date:2/7/2011

A team of researchers at the University of Gothenburg, Sweden, has identified an enzyme that protects against inflammation and joint destruction. Made when the researchers blocked production of the enzyme GGTase-I in transgenic mice, this unexpected discovery could lead to the identification of new mechanisms that control the development of inflammatory disorders, as well as new medicines.

The article has been published in the Journal of Clinical Investigation (JCI). GGTase-I is found in all cells but is particularly important for the function of so-called CAAX proteins in inflammatory cells. GGTase-I attaches a cholesterol-like fatty acid on the CAAX proteins.

Researchers previously believed that this fatty acid played an important role in activating the proteins and could contribute to the functioning of inflammatory cells. There are now medicines that include substances that suppress the activity of GGTase-I with the aim of stopping the CAAX proteins from working. These substances are already being clinically tested on cancer patients, and researchers have also wondered whether they could be used to alleviate inflammatory disorders such as rheumatoid arthritis.

However, treatment with substances that inhibit GGTase-I has often been non-specific, making it difficult for researchers to assess the real potential of GGTase-I as a drug target.

"We therefore developed genetic strategies in transgenic mice to switch off the gene that codes for GGTase-I," says PhD student Omar Khan who is heading up the study along with professor Martin Berg and co-worker docent/consultant Maria Bokarewa from the Institute of Medicine. "This allowed us to investigate whether a complete blockade of GGTase-I can inhibit the development of inflammatory disorders and whether there are any side-effects."

However, the results were quite the opposite of what the researchers were expecting. Instead of inhibiting inflammation, the deficiency of GG
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Contact: Omar Khan
omar.khan@wlab.gu.se
46-031-342-4723
University of Gothenburg
Source:Eurekalert

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