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. 2005 Feb;166(2):511–520. doi: 10.1016/S0002-9440(10)62273-0

Figure 9.

Figure 9

The TWEAK-Fn14 signaling system may play a role in stroke pathophysiology. We have shown here that focal cerebral ischemia promotes an increase in TWEAK and Fn14 expression in the ischemic penumbra. We propose that TWEAK binding to Fn14 cell surface receptors would then induce TNFR-associated factor (TRAF) 1, 2, 3, and 5 binding to the TRAF binding site (TBS) on the Fn14 cytoplasmic tail.15 NF-κB, ERK, and/or JNK pathway activation17 would then stimulate cellular production of proinflammatory cytokines and apoptotic factors, resulting in neurotoxicity and brain injury. We hypothesize that administration of the soluble Fn14-Fc decoy receptor into the brain prevents endogenous TWEAK from binding to Fn14 cell surface receptors and thereby reduces ischemia-mediated cell death.