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 Scientists unlock ability to generate new sensory hair cells
22.02.2017 | Brigham and Women's Hospital

nachricht New insights into the information processing of motor neurons
22.02.2017 | Max Planck Florida Institute for Neuroscience

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Microhotplates for a smart gas sensor

22.02.2017 | Power and Electrical Engineering

Scientists unlock ability to generate new sensory hair cells

22.02.2017 | Life Sciences

Prediction: More gas-giants will be found orbiting Sun-like stars

22.02.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>