Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The flexible tail of the prion protein poisons brain cells

01.08.2013
For decades, there has been no answer to the question of why the altered prion protein is poisonous to brain cells.

Neuropathologists from the University of Zurich and University Hospital Zurich have now shown that it is the flexible tail of the prion protein that triggers cell death. These findings have far-reaching consequences: only those antibodies that target the tail of the prion protein are suitable as potential drugs for combating prion diseases.

Prion proteins are the infectious pathogens that cause Mad Cow Disease and Creutzfeldt-Jakob disease. They occur when a normal prion protein becomes deformed and clumped. The naturally occurring prion protein is harmless and can be found in most organisms. In humans, it is found in our brain cell membrane. By contrast, the abnormally deformed prion protein is poisonous for the brain cells.

Adriano Aguzzi, Professor of Neuropathology at the University of Zurich and University Hospital Zurich, has spent many years exploring why this deformation is poisonous. Aguzzi’s team has now discovered that the prion protein has a kind of «switch» that controls its toxicity. This switch covers a tiny area on the surface of the protein. If another molecule, for example an antibody, touches this switch, a lethal mechanism is triggered that can lead to very fast cell death.

Flexible tail induces cell death

In the current edition of «Nature», the scientists demonstrate that the prion protein molecule comprises two functionally distinct parts: a globular domain, which is tethered to the cell membrane, and a long and unstructured tail. Under normal conditions, this tail is very important in order to maintain the functioning of nerve cells. By contrast, in the case of a prion infection the pathogenic prion protein interacts with the globular part and the tail causes cell death – this is the hypothesis put forward by the researchers.

Aguzzi and his team tested this by generating mimetic antibodies in tissue sections from the cerebellum of mice which have a similar toxicity to that of a prion infection. The researchers found that these antibodies tripped the switch of the prion protein. «Prion proteins with a trimmed version of the flexible tail can, however, no longer damage the brain cells, even if their switch has been recognized by antibodies», explains Adriano Aguzzi. «This flexible tail is responsible for causing cell death.» If the tail is bound and made inaccessible using a further antibody, activation of the switch can likewise no longer trigger cell death.

«Our discovery has far-reaching consequences for understanding prion diseases», says Aguzzi. The findings reveal that only those antibodies that target the prion protein tail are suitable for use as potential drugs. By contrast, antibodies that trip the switch of the prion are very harmful and dangerous.

Literature:
Tiziana Sonati, Regina R. Reimann, Jeppe Falsig, Pravas Kumar Baral, Tracy O’Connor, Simone Hornemann, Sine Yaganoglu, Bei Li, Uli S. Herrmann, Barbara Wieland, Mridula Swayampakula, Muhammad Hafizur Rahman, Dipankar Das, Nat Kav, Roland Riek, Pawel P. Liberski, Michael N. G. James, and Adriano Aguzzi. The flexible tail of the prion protein mediates the toxicity of antiprion antibodies. Nature. July 31, 2013. Doi: 10.1038/nature12402
Contacts:
Prof. Adriano Aguzzi
Institute of Neuropathology
University of Zurich
Phone: +41 44 255 21 07
E-mail: adriano.aguzzi@usz.ch
Weitere Informationen:
http://www.mediadesk.uzh.ch/articles/2013/der-flexible-schweif-des-prions-vergiftet-hirnzellen_en.html

– News release of the University of Zurich in English, including video

http://www.mediadesk.uzh.ch/articles/2013/der-flexible-schweif-des-prions-vergiftet-hirnzellen.html

– News release of the University of Zurich in German, including video

Beat Müller | Universität Zürich
Further information:
http://www.usz.ch

More articles from Life Sciences:

nachricht Toward a 'smart' patch that automatically delivers insulin when needed
18.01.2017 | American Chemical Society

nachricht 127 at one blow...
18.01.2017 | Stiftung Zoologisches Forschungsmuseum Alexander Koenig, Leibniz-Institut für Biodiversität der Tiere

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

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...

Im Focus: Studying fundamental particles in materials

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...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

A big nano boost for solar cells

18.01.2017 | Power and Electrical Engineering

Glass's off-kilter harmonies

18.01.2017 | Materials Sciences

Toward a 'smart' patch that automatically delivers insulin when needed

18.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>