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Enzymes implicated in disease processes attack one another instead of harming body proteins
Date:8/13/2012

Researchers for the first time have shown that members of a family of enzymes known as cathepsins which are implicated in many disease processes may attack one another instead of the bodily proteins they normally degrade. Dubbed "cathepsin cannibalism," the phenomenon may help explain problems with drugs that have been developed to inhibit the effects of these powerful proteases.

Cathepsins are involved in disease processes as varied as cancer metastasis, atherosclerosis, cardiovascular disease, osteoporosis and arthritis. Because cathepsins have harmful effects on critical proteins such as collagen and elastin, pharmaceutical companies have been developing drugs to inhibit activity of the enzymes, but so far these compounds have had too many side effects to be useful and have failed clinical trials.

Using a combination of modeling and experiments, researchers from the Georgia Institute of Technology and Emory University have shown that one type of cathepsin preferentially attacks another, reducing the enzyme's degradation of collagen. The work could affect not only the development of drugs to inhibit cathepsin activity, but could also lead to a better understanding of how the enzymes work together.

"These findings provide a new way of thinking about how these proteases are working with and against each other to remodel tissue or fight against each other," said Manu Platt, an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. "There has been an assumption that these cathepsins have been inert in relationship to one another, when in actuality they have been attacking one another. We think this may have broader implications for other classes of proteases."

The research was supported by the National Institutes of Health, the National Science Foundation and the Georgia Cancer Coalition. Details of the study were reported August 10 in the Journal of B
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Contact: John Toon
jtoon@gatech.edu
404-894-6986
Georgia Institute of Technology Research News
Source:Eurekalert  

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