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
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:
Phone: +49(0)89-3187-3946, Fax +49(0)89-3187-3324, Internet: www.helmholtz-muenchen.de, E-mail: email@example.com
Sven Winkler | EurekAlert!
Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel
The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education
For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.
According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
23.01.2017 | Health and Medicine
23.01.2017 | Physics and Astronomy
23.01.2017 | Process Engineering