Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The Protein Srebp2 Drives Cholesterol Formation in Prion-Infected Neuronal Cells Which May Promote Prion-Dependent Diseases

20.11.2009
The regulating protein Srebp2 drives cholesterol formation, which prions need for their propagation, in prion-infected neuronal cells. With these findings, published in the current issue of the Journal of Biological Chemistry, scientists of Helmholtz Zentrum München and Technische Universität München anticipate new approaches in drug development to combat prion infection.

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 München and Technische Universität München 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 München and Technische Universität 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 the corresponding protein. If cholesterol concentration is elevated in a healthy cell, Srebp2 remains in its inactive form and does not bind to the sterol regulatory element. This control mechanism is obviously disturbed in the infected cells, causing increased cholesterol synthesis. "Remarkably, only neuronal cells react in this way – microglia cells exposed to prions do not increase their cholesterol production," said Professor Hermann Schätzl of the Institute of Virology of Technische Universität München, who led the research together with Dr. Ina Vorberg. Further studies shall elucidate what role disturbed cholesterol regulation plays in neuronal cells for the development of prion diseases and shall thus point the way to new therapy approaches.

Further Information
Original Publication
Christian Bach, Sabine Gilch, Romina Rost, Alex D. Greenwood, Marion Horsch, Glaucia N.M. Hajj, Susanne Brodesser, Axel Facius, Sandra Schädler, Konrad Sandhoff, Johannes Beckers, Christine Leib-Mösch, Hermann M. Schätzl und Ina Vorberg, Prion-Induced Activation of Cholesterogenic Gene Expression by a Sterol Regulatory Element Binding Protein (Srebp2) in Neuronal Cells, Journal Biological Chemistry Vol 284, No. 45, pp 31260-31269 Nov 2009

Helmholtz Zentrum München is the German Research Center for Environmental Health. As leading center oriented toward Environmental Health, it focuses on chronic and complex diseases which develop from the interaction of environmental factors and individual genetic disposition. Helmholtz Zentrum München has around 1680 staff members. The head office of the center is located in Neuherberg to the north of Munich on a 50-hectare research campus. Helmholtz Zentrum München belongs to the Helmholtz Association, Germany’s largest research organization, a community of 16 scientific-technical and medical-biological research centers with a total of 26,500 staff members.

At the Institute of Virology of Technische Universität München (Director: Prof. Dr. Ulrike Protzer), the prion research groups of the research area Clinical Virology (Prof. Dr. Hermann Schätzl) have for the last ten years been studying the molecular and cellular biogenesis and pathogenesis of prions, including possible therapeutic approaches. The research group of Dr. Ina Vorberg is specialized in cell culture models for studying prions and prion-like proteins.

Contact for Media Representatives:
Sven Winkler, Helmholtz Zentrum München – German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany

Phone: +49(0)89-3187-3946, Fax +49(0)89-3187-3324, Internet: www.helmholtz-muenchen.de, E-mail: presse@helmholtz-muenchen.de

Sven Winkler | EurekAlert!
Further information:
http://www.helmholtz-muenchen.de

More articles from Life Sciences:

nachricht Fingerprint' technique spots frog populations at risk from pollution
27.03.2017 | Lancaster University

nachricht Parallel computation provides deeper insight into brain function
27.03.2017 | Okinawa Institute of Science and Technology (OIST) Graduate University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Northern oceans pumped CO2 into the atmosphere

27.03.2017 | Earth Sciences

Fingerprint' technique spots frog populations at risk from pollution

27.03.2017 | Life Sciences

Big data approach to predict protein structure

27.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>