NF-kB and Inflammatory Cytokine Signalling: Role in Skeletal Muscle Atrophy

Atrophy is a classical hallmark of an array of disorders that affect skeletal muscle, ranging from inherited dystrophies, acquired inflammatory myopathies, ageing (sarcopenia) and critical illness (sepsis). The loss of muscle mass and function in these instances is associated with disability, poor quality of life and in some cases mortality. The mechanisms which underpin muscle atrophy are complex; however, significant research has demonstrated an important role for inflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha), mediated by the generation of reactive oxygen species (ROS) in muscle wasting. Moreover, activation of the transcription factor nuclear factor kappa B (NF-kappa B) is a key lynchpin in the overall processes that mediate muscle atrophy. The significance of NF-kappa B as a key regulator of muscle atrophy has been emphasised by several in vivo studies, which have demonstrated that NF-kappa B-targeted therapies can abrogate muscle atrophy. In this chapter, we will summarise current knowledge on the role of cytokines (TNF-alpha) and NF-kappa B in the loss of muscle mass and function and highlight perspectives towards future research and potential therapies to combat muscle atrophy.