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LCSB discovers endogenous antibiotic in the brain
Date:5/6/2013

came as a major surprise."

However, it was not known how mammalian cells can synthesise this compound. Through sequence comparisons of the fungi's enzyme sequence to human protein sequences, Karsten Hiller then identified a human gene, which encodes a protein similar to the one in fungi: immunoresponsive gene 1, or IRG1 for short a most exciting discovery as the function of this gene was not known. Says Hiller: "When it comes to IRG1, there is a lot of uncharted territory. What we did know is that it seems to play some role in the big picture of the immune response, but what exactly that role was, we were not sure."

To change this situation, the team turned off IRG1 in cell cultures and instead added the gene to cells that normally do not express it. The experiments confirmed that in mammals, IRG1 codes for an itaconic acid-producing enzyme. But why? When immune cells like macrophages and microglial cells take up bacteria in order to inactivate them, the intruders are actually able to survive by using a special metabolic pathway called the glyoxylate shunt. According to Hiller, "macrophages produce itaconic acid in an effort to foil this bacterial survival strategy.

The acid blocks the first enzyme in the glyoxylate pathway. Which is how macrophages partially inhibit growth in order to support the innate immune response and digest the bacteria they have taken up." LCSB director Prof. Dr. Rudi Balling describes the possibilities that these insights offer: "Parkinson's disease is highly complex and has many causes. We now intend to study the importance of infections of the nervous system in this respect and whether itaconic acid can play a role in diagnosing and treating Parkinson's disease."


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Contact: karsten.hiller@uni.lu
karsten.hiller@uni.lu
352-466-644-6136
University of Luxembourg
Source:Eurekalert

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