Stay-at-home transcription factor prevents neurodegeneration

October 29, 2012
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.

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, 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 has accumulated that treatments won't work. 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 " 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 , 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 .

Explore further: Nerve pathway for combating axon injury and stress may hold benefits for individuals with neurodegenerative disorders

More information: J. Cell Biol. doi:10.1083/jcb.201203109

Related Stories

Nerve pathway for combating axon injury and stress may hold benefits for individuals with neurodegenerative disorders

June 27, 2012
(Medical Xpress) -- Researchers from the Huck Institutes' Center for Cellular Dynamics — led by Center director Melissa Rolls — have found that a neuroprotective pathway initiated in response to injured or stressed ...

New drug target for kidney disease discovered

April 26, 2011
Two discoveries at UC Santa Barbara point to potential new drug therapies for patients with kidney disease. The findings are published in this week's issue of the Proceedings of the National Academy of Sciences.

Recommended for you

Estrogen discovery could shed new light on fertility problems

December 12, 2017
Estrogen produced in the brain is necessary for ovulation in monkeys, according to researchers at the University of Wisconsin-Madison who have upended the traditional understanding of the hormonal cascade that leads to release ...

Time of day affects severity of autoimmune disease

December 12, 2017
Insights into how the body clock and time of day influence immune responses are revealed today in a study published in leading international journal Nature Communications. Understanding the effect of the interplay between ...

3-D printed microfibers could provide structure for artificially grown body parts

December 12, 2017
Much as a frame provides structural support for a house and the chassis provides strength and shape for a car, a team of Penn State engineers believe they have a way to create the structural framework for growing living tissue ...

Team identifies DNA element that may cause rare movement disorder

December 11, 2017
A team of Massachusetts General Hospital (MGH) researchers has identified a specific genetic change that may be the cause of a rare but severe neurological disorder called X-linked dystonia parkinsonism (XDP). Occurring only ...

Protein Daple coordinates single-cell and organ-wide directionality in the inner ear

December 11, 2017
Humans inherited the capacity to hear sounds thanks to structures that evolved millions of years ago. Sensory "hair cells" in the inner ear have the amazing ability to convert sound waves into electrical signals and transmit ...

Gene therapy improves immunity in babies with 'bubble boy' disease

December 9, 2017
Early evidence suggests that gene therapy developed at St. Jude Children's Research Hospital will lead to broad protection for infants with the devastating immune disorder X-linked severe combined immunodeficiency disorder. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.