Nuclear factor-κB signalling and transcriptional regulation in skeletal muscle atrophy

The nuclear factor-κB (NF-κB) signalling pathway is a necessary component of adult skeletal muscle atrophy resulting from systemic illnesses or disuse. Studies showing a role for the NF-κB pathway in muscle disuse include unloading, denervation and immobilization, and studies showing a role for NF-κB in systemic illnesses include cancer, chronic heart failure and acute septic lung injury. Muscle atrophy due to most of these triggers is associated with activation of NF-κB transcriptional activity. With the exception of muscle unloading, however, there is a paucity of data on the NF-κB transcription factors that regulate muscle atrophy, and little is known about which genes are targeted by NF-κB transcription factors during atrophy. Interestingly, in some cases it appears that the amelioration of muscle atrophy by genetic inhibition of NF-κB signalling proteins is due to effects that are independent of the downstream NF-κB transcription factors. These questions are prime areas for investigation if we are to understand a key component of muscle wasting in adult skeletal muscle.