Role for IKK2 in muscle: waste not, want not

Activation of transcription factor NF-kappa B, the major regulator of the inflammatory response, depends on the inhibitor of NF-kappa B kinase (IKK) complex, which is composed of 2 catalytic subunits, IKK1 and IKK2 (also known as IKK alpha and IKK beta), and a regulatory subunit, IKK gamma (also known as NEMO). In this issue of the JCI, Mourkioti et al. show that muscle-specific disruption in mice of the gene encoding IKK2 prevents NF-kappa B activation in response to denervation or toxin-induced injury (see the related article beginning on page 2945). Importantly, this genetic manipulation prevents muscle wasting, thereby providing strong evidence in support of a major pathogenic role for inflammation in a variety of muscular dystrophies characterized by progressive muscle fliber degeneration.