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The protein Srebp2 drives cholesterol formation in prion-infected neuronal cells
Date:11/18/2009

Prions are causing fatal and infectious diseases of the nervous system, such as the mad cow disease (BSE), scrapie in sheep or Creutzfeldt-Jakob disease in humans. Scientists of Helmholtz Zentrum Mnchen and Technische Universitt Mnchen have now succeeded in elucidating another disease mechanism of prion diseases: The prion-infected cell changes its gene expression and produces increased quantities of cholesterol. Prions need this for their propagation.

Prions are infectious and transform the brains of humans and animals into sponge-like structures. Unlike a virus, a prion only consists of protein - called prion-protein in its pathological form (PrPSc). Until now, little was known about the processes that take place inside the infected neuronal cell. This made it difficult to develop effective drugs against prion diseases.

Using microarrays developed in the lab of Dr. Johannes Beckers, Christian Bach and colleagues from Helmholtz Zentrum Mnchen and Technische Universitt made a genome-wide analysis of gene activity in prion-infected and healthy cells. The researchers found over 100 genes which are differentially expressed in infected and healthy cells. This has serious consequences for the infected cells: "Several enzymes of cholesterol biosynthesis are affected", explained Christian Bach, first author of the study. As a consequence, the cholesterol level rises in the infected cells.

The cause of this development is the increased activity of the regulating protein Srebp2. It switches on the genes that are involved in cholesterol biosynthesis and cellular uptake. To achieve this, Srebp2 binds to a special segment encoding the gene to be transcribed - the sterol regulatory element. This activates the gene, leading to the biosynthesis of the corresponding protein.

In every step of cholesterol biosynthesis Srebp2 switches on different genes, thus exactly controlling gene expression, i.e. the translation of gene information into
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Contact: Sven Winkler
presse@helmholtz-muenchen.de
49-089-318-73946
Helmholtz Zentrum Mnchen - German Research Center for Environmental Health
Source:Eurekalert

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