Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New clue to nerve growth may help regeneration efforts

17.12.2004


Johns Hopkins scientists have discovered how one family of proteins repels growing nerves and keeps them properly on track during development. The finding, described in the Dec. 16 issue of Neuron, might provide a chance to overcome the proteins’ later role in preventing regrowth of injured nerves, the researchers say.

The proteins, known as chondroitin sulfate proteoglycans (CSPGs), have long been known to prevent nerve regeneration after injury by recruiting a stew of other proteins and agents, but exactly what part of the mix keeps nerves from regrowing is unknown.

In studies of nerve growth in developing rats, the Hopkins scientists have linked CSPGs’ no-growth effects to a protein called semaphorin 5A. The scientists, including David Kantor, an M.D./Ph.D. candidate, found that when CSPGs bind to semaphorin 5A, growing nerves are stopped in their tracks. Blocking this particular interaction freed the nerves to continue growing.



"CSPGs are a critical obstacle to nerve regeneration after injury, and without details about what’s really happening, it’s impossible to rationally intervene," says study leader Alex Kolodkin, Ph.D., professor of neuroscience in Johns Hopkins’ Institute for Basic Biomedical Sciences. "We studied nerve growth, rather than re-growth, but our work provides a starting point for identifying more partners of CSPGs and for finding targets to try to counter these proteins’ effects in nerve regeneration."

Semaphorins, including 5A, are a family of proteins that help direct growing nerves as they extend toward their eventual targets, largely by keeping nerves out of places they shouldn’t be.

"These proteins are classic ’guidance cues’ for nerves. There’s nothing particularly fancy about what they do -- they bind to spots on the tip of the growing nerve, and the nerve doesn’t continue going in that direction," says Kolodkin, whose lab studies semaphorins. "Scientists studying CSPGs’ effects haven’t really been considering classic guidance cues as CSPGs’ key partners, but our study suggests they just might be."

When a nerve is damaged, large amounts of CSPG proteins accumulate at the site of injury. These proteins, in turn, draw in a host of other factors, including semaphorins. Others have shown that without CSPGs, damaged nerves growing in a dish can regenerate, a finding that suggests blocking CSPGs might permit the same in animals.

In experiments in laboratory dishes, Kantor simulated a particular step in the brain development of developing rats. During this step, specific nerves begin connecting between what will eventually be two sections of the brain.

Because the accurate extension of these nerves requires semaphorin 5A, Kantor was able to identify key molecules that interact with it. He found that CSPGs bind semaphorin 5A to prevent nerves from extending across a no-man’s-land between the nerves’ simulated origin and target. Preventing this interaction by adding an enzyme that destroys only CSPGs allowed nerves to penetrate that space when they shouldn’t have.

Kantor also found that semaphorin 5A helps keep the bundle of growing nerve fibers together by interacting with a different family of proteins, those known as heparan sulfate proteoglygans (HSPGs). Other semaphorins also are known to have the apparent paradox of both encouraging growth and restricting it.

"Semaphorins’ dual abilities likely stem in part from interactions with different partners, as we’ve seen here," says Kolodkin, whose team is now studying how semaphorin 5A’s signal and binding partners change, and whether it also partners with CSPGs to suppress regeneration. "During development, the available partners change with time and place, helping a limited number of guidance cues accomplish a very complex task."

The Hopkins researchers were funded by the Johns Hopkins Medical Scientist Training Program, the Christopher Reeve Paralysis Foundation, and the National Institute of Neurological Disorders and Stroke.

Authors on the paper are Kantor, Kolodkin and Katherine Peer of Johns Hopkins; Onanong Chivatakarn and Roman Giger of the University of Rochester, NY; Stephen Oster and David Sretavan, University of California, San Francisco; Masaru Inatani and Yu Yamaguchi, The Burnham Institute, La Jolla, Calif.; and Michael Hansen and John Flanagan, Harvard Medical School.

Joanna Downer | EurekAlert!
Further information:
http://www.neuron.org/
http://www.jhmi.edu

More articles from Health and Medicine:

nachricht GLUT5 fluorescent probe fingerprints cancer cells
20.04.2018 | Michigan Technological University

nachricht Scientists re-create brain neurons to study obesity and personalize treatment
20.04.2018 | Cedars-Sinai Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: BAM@Hannover Messe: innovative 3D printing method for space flight

At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.

Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...

Im Focus: Molecules Brilliantly Illuminated

Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.

Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Quantum Technology for Advanced Imaging – QUILT

24.04.2018 | Information Technology

AWI researchers measure a record concentration of microplastic in arctic sea ice

24.04.2018 | Earth Sciences

Complete skin regeneration system of fish unraveled

24.04.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>