Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stay-at-home transcription factor prevents neurodegeneration

30.10.2012
A study in The Journal of Cell Biology shows how a transcription factor called STAT3 remains in the axon of nerve cells to help prevent neurodegeneration. The findings could pave the way for future drug therapies to slow nerve damage in patients with neurodegenerative diseases.

In Lou Gehrig's Disease (ALS) and other neurodegenerative diseases, nerve cells usually die in stages, with axons deteriorating first and the cells themselves perishing later. Axon degeneration may represent a turning point for patients, after which so much nerve damage has accumulated that treatments won't work.


A JCB study shows how the protein CNTF activates the transcription factor STAT3 (green), which lingers in the axon (blue) and helps stabilize microtubules by inhibiting a protein called stathmin (magenta). STAT3 and stathmin colocalize in axonal branch points (arrowheads) and growth cones (arrow).

Credit: Selvaraj, B.T., et al. 2012. J. Cell Biol. doi:10.1083/jcb.201203109

Researchers have tested several proteins for their ability to save axons. One of these molecules, CNTF, rescues axons in rodents and extends their lives. But it caused severe side effects in patients during clinical trials. "Acting on the same pathway but farther downstream could be an ideal way to improve the situation for motor neuron disease" and possibly for other neurodegenerative diseases, says senior author Michael Sendtner from the University of Wuerzburg in Germany.

To discover how CNTF works, Sendtner and his colleagues studied mice with a mutation that mimics ALS. The researchers found that CNTF not only prevented shrinkage of the rodents' motor neurons, it also reduced the number of swellings along the axon that are markers of degeneration. It is known that CNTF indirectly turns on the transcription factor STAT3, so the researchers wanted to determine if STAT3 is behind CNTF's protective powers. They tested whether CNTF helps motor neurons that lack STAT3 and discovered that, in the mutant mice, axons lacking STAT3 were half as long as those from a control group after CNTF treatment

Once it has been activated, STAT3 typically travels to the nucleus of the neuron to switch on genes. But the researchers were surprised to find that most of the axonal STAT3 did not move to the nucleus and instead had a local effect in the axon. Specifically, the team found that activated STAT3 inhibited stathmin, a protein that normally destabilizes microtubules. When the team removed stathmin in motor neurons from the mutant mice, the axons grew at the same rate as axons from normal mice but didn't elongate any faster after doses of CNTF. These results indicate that CNTF mainly stimulates axon growth by thwarting stathmin and suggests that drugs to block stathmin could slow neuron breakdown in patients with neurodegenerative diseases.

About The Journal of Cell Biology (JCB)

JCB is published by The Rockefeller University Press. All editorial decisions on manuscripts submitted are made by active scientists in conjunction with our in-house scientific editors. JCB content is posted to PubMed Central, where it is available to the public for free six months after publication. Authors retain copyright of their published works, and third parties may reuse the content for non-commercial purposes under a creative commons license. For more information, please visit www.jcb.org.

Selvaraj, B.T., et al. 2012. J. Cell Biol. doi:10.1083/jcb.201203109

Rita Sullivan King | EurekAlert!
Further information:
http://www.rupress.org
http://www.jcb.org

More articles from Life Sciences:

nachricht Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel

nachricht The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

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...

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

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>