Tweak and FN14 in central nervous system health and disease

The tumor necrosis factor superfamily (TNFSF) of cytokines comprises 19 ligands and 28 receptors (1). Ligand-mediated activation of TNFSF receptors plays a role in the pathogenesis of multiple central nervous system (CNS) diseases such as multiple sclerosis (2) and cerebral ischemia (3). Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the TNFSF (4) that binds a small cell surface receptor known as fibroblast growth factor-inducible 14 (Fn14) (5-7). There is a growing body of evidence indicating that the interaction between TWEAK and Fn14 plays a role on cell death, regulation of the permeability of the neurovascular unit (NVU) and development of an inflammatory response in the CNS under physiological and pathological conditions (8, 9). Accordingly, here we will review the information available to this date on the role of this cytokine and its receptor in the CNS.