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The TWEAK-Fn14 cytokine-receptor axis: discovery, biology and therapeutic targeting Winkles JANat Rev Drug Discov 2008[May]; 7 (5): 411-25TWEAK is a multifunctional cytokine that controls many cellular activities including proliferation, migration, differentiation, apoptosis, angiogenesis and inflammation. TWEAK acts by binding to Fn14, a highly inducible cell-surface receptor that is linked to several intracellular signalling pathways, including the nuclear factor-kappaB (NF-kappaB) pathway. The TWEAK-Fn14 axis normally regulates various physiological processes, in particular it seems to play an important, beneficial role in tissue repair following acute injury. Furthermore, recent studies have indicated that TWEAK-Fn14 axis signalling may contribute to cancer, chronic autoimmune diseases and acute ischaemic stroke. This Review provides an overview of TWEAK-Fn14 axis biology and summarizes the available data supporting the proposal that both TWEAK and Fn14 should be considered as potential targets for the development of novel therapeutics.|*Signal Transduction[MESH]|Animals[MESH]|Cytokines/metabolism[MESH]|Humans[MESH]|Neoplasms/*therapy[MESH]|Receptors, Tumor Necrosis Factor/*physiology[MESH]|TWEAK Receptor[MESH] |
