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

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Researchers invent tiny, light-powered wires to modulate brain's electrical signals

21.02.2018 | Life Sciences

The “Holy Grail” of peptide chemistry: Making peptide active agents available orally

21.02.2018 | Life Sciences

Atomic structure of ultrasound material not what anyone expected

21.02.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>