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 co