Commun Biol . 2026 Apr 2;9(1):726. doi: 10.1038/s42003-026-09975-3. TWEAK-induced alternative NF-κB signaling regulates Cxcl10 and Mymx to promote myoblast-to-myotube fusion and muscle regeneration

The NF-κB pathway has emerged as an important signaling network in skeletal muscle. Depending on the type of stimulus, activation of NF-κB signaling can occur through the classical or alternative pathway.

TWEAK is a membrane bound and soluble cytokine that signals through Fn14, a highly inducible cell-surface receptor that is upstream of numerous signaling pathways including NF-κB. Upregulation of Fn14 signaling is associated with the progression of several chronic atrophic muscle disorders. In contrast, TWEAK/Fn14 signaling has also been suggested to play a beneficial role during muscle regeneration by promoting myoblast proliferation and fusion.