TWEAK triggers atrophy of disused muscle

Mar 22, 2010
Muscle fibers grow smaller after denervation (left), but are protected when TWEAK activity is inhibited by a neutralizing antibody (right). Credit: Mittal, A., et al. 2010. J. Cell Biol. doi:10.1083/jcb.200909117.

A new study in the Journal of Cell Biology (JCB) identifies a cytokine signaling pathway that induces the breakdown of disused skeletal muscle. Blocking this pathway could prevent immobilized patients from losing their muscle tissue.

Skeletal muscle wastes away when its activity is reduced by, for example, a injury. Although the mechanism by which muscle fibers break down is understood fairly well, how the process is triggered remains unknown. The TNF-related cytokine TWEAK can induce muscle loss, but whether it does so in disused muscle is unclear.

A team led by Ashok Kumar (University of Louisville School of Medicine, Kentucky) compared how mice expressing different amounts of TWEAK responded when the nerve innervating their hind legs was severed. Mice producing excess TWEAK lost their muscle more quickly than wild-type animals, whereas mice lacking this cytokine were largely protected from muscle breakdown. TWEAK levels also correlated with the amount of , another common symptom of muscle disuse. Inhibiting TWEAK with a neutralizing antibody was sufficient to block muscle breakdown following the loss of motor neurons, suggesting that the pathway could be a viable therapeutic target.

The article appears in the March 22 issue of the .

Explore further: New compounds protect nervous system from the structural damage of MS

More information: Mittal, A., et al. 2010. J. Cell Biol. doi:10.1083/jcb.200909117

add to favorites email to friend print save as pdf

Related Stories

'Mighty mice' made mightier

Aug 29, 2007

The Johns Hopkins scientist who first showed that the absence of the protein myostatin leads to oversized muscles in mice and men has now found a second protein, follistatin, whose overproduction in mice lacking ...

Team identifies stem cells that repair injured muscles

Mar 05, 2009

A University of Colorado at Boulder research team has identified a type of skeletal muscle stem cell that contributes to the repair of damaged muscles in mice, which could have important implications in the treatment of injured, ...

FHL1 helps build muscle mass

Dec 15, 2008

Cowling et al. report how to build muscle mass with FHL1. The protein partners with and activates the transcription factor, NFATc1. Encouraging this partnership might provide a possible treatment for muscle ...

Recommended for you

Mystery of the reverse-wired eyeball solved

Feb 27, 2015

From a practical standpoint, the wiring of the human eye - a product of our evolutionary baggage - doesn't make a lot of sense. In vertebrates, photoreceptors are located behind the neurons in the back of the eye - resulting ...

Neurons controlling appetite made from skin cells

Feb 27, 2015

Researchers have for the first time successfully converted adult human skin cells into neurons of the type that regulate appetite, providing a patient-specific model for studying the neurophysiology of weight ...

Quality control for adult stem cell treatment

Feb 27, 2015

A team of European researchers has devised a strategy to ensure that adult epidermal stem cells are safe before they are used as treatments for patients. The approach involves a clonal strategy where stem cells are collected ...

User comments : 0

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.