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 Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

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

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>