Researchers illustrate how muscle growth inhibitor is activated, could aid in treating ALS

January 19, 2018, University of Cincinnati Academic Health Center
Thomas Thompson, PhD, is shown in his laboratory at the University of Cincinnati College of Medicine. Credit: University of Cincinnati College of Medicine

Researchers at the University of Cincinnati (UC) College of Medicine are part of an international team that has identified how the inactive or latent form of GDF8, a signaling protein also known as myostatin responsible for limiting muscle, is activated.

That knowledge could someday help in finding a better treatment to improve in diseases such as , (ALS) or Lou Gehrig's disease, and cancer cachexia, a wasting condition, says Tom Thompson, PhD, professor in the UC Department of Molecular Genetics, Biochemistry and Microbiology. Muscular Dystrophy is a hereditary condition marked by weakness and progressive wasting of the muscles, while ALS impacts nerve cells that control voluntary muscle movement.

The research team's findings are detailed in a peer-reviewed article in the scholarly journal for the Proceedings of the National Academy of Sciences (PNAS). Thompson is the corresponding author for the journal article, "Molecular Characterization of Latent GDF8 Reveals Mechanisms of Activation," and its first author, Ryan Walker, is a postdoctoral fellow at Harvard University and a former UC doctoral student who once worked in Thompson's laboratory. Also from UC participating in the study are Jason McCoy, a doctoral student, and Magdalena Czepnik, a research assistant.

"All animals have the protein molecule which limits the size of our muscle," explains Thompson. "Myostatin is being targeted therapeutically to boost muscle production in patients with muscle disorders."

"Myostatin is one member in this very large family of that includes 33 ligands. They play very important roles in many aspects of the human body and often are wrongly regulated in many human diseases such as cancer. Some are used to develop bone while others play large roles during in human reproduction."

During synthesis, GDF8 or myostatin, is made as a precursor which remains in a dormant state with half of the molecule holding the section of GDF8 responsible for signaling inactive, says Thompson. Activation involves slicing a section of the molecule responsible for dormancy, thus allowing signaling to occur in myostatin and inhibition of . Researchers were able to demonstrate that myostatin could be turned on with minor changes to the molecule's dormant mechanism.

"As researchers, our goal is to understand the details of how these molecules are locked," says Thompson, adding that they will be using animal models to conduct this research. "By tweaking the dormant state of the molecule, we can get myostatin to signal without the need for cutting, basically picking the lock without a key. Our study illustrates what parts of the dormant state are important for holding GDF8 inactive and can be helpful in understanding the mechanism for GDF8 signaling."

Explore further: Muscle growth finding may assist with cancer treatment

More information: Ryan G. Walker et al. Molecular characterization of latent GDF8 reveals mechanisms of activation, Proceedings of the National Academy of Sciences (2018). DOI: 10.1073/pnas.1714622115

Related Stories

Muscle growth finding may assist with cancer treatment

June 13, 2017
Monash University's Biomedicine Discovery Institute (BDI) researchers have collaboratively developed a therapeutic approach that dramatically promotes the growth of muscle mass, which could potentially prevent muscle wasting ...

One step closer to an 'exercise pill'

April 25, 2017
Suppressing production of the protein myostatin enhances muscle mass and leads to significant improvements in markers of heart and kidney health, according to a study conducted in mice. Joshua T. Butcher, PhD, a postdoctoral ...

Possible muscle disease therapeutic target found

August 6, 2012
The study of muscular system protein myostatin has been of great interest to researchers as a potential therapeutic target for people with muscular disorders. Although much is known about how myostatin affects muscle growth, ...

Researchers solve key part of old mystery in generating muscle mass

September 27, 2012
Working with mice, Johns Hopkins researchers have solved a key part of a muscle regeneration mystery plaguing scientists for years, adding strong support to the theory that muscle mass can be built without a complete, fully ...

Recommended for you

Team develops new way to grow blood vessels

August 17, 2018
Formation of new blood vessels, a process also known as angiogenesis, is one of the major clinical challenges in wound healing and tissue implants. To address this issue, researchers from Texas A&M University have developed ...

New imaging technique can spot tuberculosis infection in an hour

August 16, 2018
Guided by glowing bacteria, researchers have devised an imaging technique that can diagnose live tuberculosis in an hour and help monitor the efficacy of treatments. That's particularly critical because many TB strains have ...

Obesity, infertility and oxidative stress in mouse egg cells

August 16, 2018
Excessive body fat is associated with negative effects on female fertility and pregnancy. In mice, maternal obesity impairs proper development of egg precursor cells called oocytes. In a recent paper published in Molecular ...

Research shows it's possible to reverse damage caused by aging cells

August 15, 2018
What's the secret to aging well? University of Minnesota Medical School researchers have answered it- on a cellular level.

This matrix delivers healing stem cells to injured elderly muscles

August 15, 2018
A car accident leaves an aging patient with severe muscle injuries that won't heal. Treatment with muscle stem cells from a donor might restore damaged tissue, but doctors are unable to deliver them effectively. A new method ...

Male tobacco smokers have brain-wide reduction of CB1 receptors

August 15, 2018
Chronic, frequent tobacco smokers have a decreased number of cannabinoid CB1 receptors, the "pot receptor", when compared with non-smokers, reports a study in Biological Psychiatry.

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.