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 What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society

nachricht Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

What the world's tiniest 'monster truck' reveals

23.08.2017 | Life Sciences

Treating arthritis with algae

23.08.2017 | Life Sciences

Witnessing turbulent motion in the atmosphere of a distant star

23.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>