Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Knocked out in Mice: Cause for Massive Cell Death after Spinal Cord Injury

16.10.2007
Researchers now Work on Drug Development

Neurons die en masse when the spinal cord is injured or when a person suffers a stroke. Researchers of the Max Delbrueck Center for Molecular Medicine (MDC) Berlin-Buch, Germany, and of Aarhus University, Denmark, have unraveled the molecular mechanism which causes the death not only of damaged neurons, but also of healthy nerve cells.

In animal experiments, they have now been able to demonstrate that neuronal cell death can be reduced when the gene of one the key players in this process is knocked out. The research results of Professor Thomas E. Willnow (MDC) and Professor Anders Nykjaer (Aarhus University) have been published online in Nature Neuroscience (DOI: 10.1038/nn2000)*. Now they are working on the development of drugs to limit neuronal cell death after spinal cord injury.

After injury, neurons secrete the precursor protein proNGF. (The abbreviation stands for pro-nerve growth factor). ProNGF binds to a receptor called sortilin, situated on the surface of all neurons whether they are injured or not.

... more about:
»Aarhus »Neuronal »Nykjaer »Sortilin »Willnow »proNGF »spinal

As soon as proNGF binds to sortilin, it induces the lethal cascade. This explains why proNGF not only promotes the death of damaged neurons, but also of the surrounding healthy tissue.

In the embryo, inducing death of neurons is an absolutely necessary process. It keeps the developing nervous system under control. For the adult organism, however, this "deadly activity" is disastrous.

It not only causes the massive death of injured neurons, but also kills the healthy nerve cells. "This shows that neurons not only die because of the initial insult, such as lack of oxygen in stroke. To a large extent, nerve cells also die as a consequence of proNGF's binding to sortilin," Dr. Willnow explains.

With a technology for which three scientists in the US and UK have just won the Nobel Prize, Dr. Willnow and Dr. Nykjaer bred mice in which they silenced the gene for sortilin. They could show that in knock-out mice lacking sortilin, most neurons survive spinal cord injury. By contrast, in mice still expressing sortilin on the surface, up to 40 percent of the affected nerve cells are lost.

Perfect Targets
Dr. Willnow is convinced that proNGF and sortilin are perfect targets for drug development. "If the receptor sortilin can be blocked by a drug to prevent proNGF from binding to it, patients with spinal cord injuries can be treated and damage to neuronal tissue can be reduced," he says.

Researchers assume that proNGF also induces neuronal cell death in diseases such as stroke, multiple sclerosis, Alzheimer's and Parkinson's disease. "However, there is no 'proof of principle' in a mouse model as yet. That is, we cannot tell if blocking sortilin reduces neuronal cell death in these diseases, too. We are working on this problem, but it still may take a while to find the right answer," Dr. Willnow adds.

The research Dr. Willnow and Dr. Nykjaer now present in Nature Neuroscience is the result of a relatively short research period. It was not until 2001 that researchers in the US identified proNGF as the cause of neuronal cell death. At that time, the mechanism was still unknown. Only a few years later, in 2004, Dr. Willnow and Dr. Nykjaer were able to demonstrate that proNGF causes neuronal cell death by binding to sortilin.

*Roles for the pro-neurotrophin receptor sortilin in neuronal development, aging and brain injury

Pernille Jansen1, Klaus Giehl1,2, Jens R. Nyengaard3, Kenneth Teng4, Oleg Lioubinski5, Susanne S. Sjoegaard1, Tilman Breiderhoff5, Michael Gotthardt5, Fuyu Lin1, Andreas Eilers5, Claus M. Petersen1, Gary R. Lewin5, Barbara L. Hempstead4, Thomas E. Willnow5,* and Anders Nykjaer1,*.

1MIND Center, Department of Medical Biochemistry, Aarhus University, Denmark;
2Southwestern Medical Center, Dallas, TX, USA;
3MIND Center, Stereology and Electron
Microscopy Research Laboratory, Aarhus University, Denmark;
4Weill Medical College of Cornell University, New York, NY, USA;
5Max Delbrueck Center for Molecular Medicine,
Berlin, Germany.
Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Straße 10; 13125 Berlin; Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax: +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de

Barbara Bachtler | idw
Further information:
http://www.mdc-berlin.de/englisch/about_the_mdc/public_relations/e_index.htm
http://www.nature.com/neuro/journal/vaop/ncurrent/index.html
http://www.mdc-berlin.de/willnow/

Further reports about: Aarhus Neuronal Nykjaer Sortilin Willnow proNGF spinal

More articles from Life Sciences:

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

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...

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | 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

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>