TWEAK triggers atrophy of disused muscle

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TWEAK triggers atrophy of disused muscle

http://www.eurekalert.org/pub_releases/2010-03/rup-tta031210.php

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. The

article appears in the March 22 issue of the JCB (www.jcb.org).

Skeletal muscle wastes away when its activity is reduced by, for example, a

spinal cord 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 fibrosis, 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.