Skeletal muscle diseases, inflammation, and NF-kappaB signaling: insights and opportunities for therapeutic intervention.

Signaling through nuclear factor-kappa B (NF-kappaB) is emerging as an important regulator of muscle development, maintenance, and regeneration. Classic signaling modulates early muscle development by enhancing proliferation and inhibiting differentiation, and alternative signaling promotes myofiber maintenance and metabolism. Likewise, NF-kappaB signaling is critical for the development of immunity. Although these processes occur normally, dysregulation of NF-kappaB signaling has prohibitive effects on muscle growth and regeneration and can perpetuate inflammation in muscle diseases. Aberrant NF-kappaB signaling from immune and muscle cells has been detected and implicated in the pathologic progression of numerous dystrophies and myopathies, indicating that targeted NF-kappaB inhibitors may prove clinically beneficial.