Together with earlier findings that TNFR1 knock-out mice develop larger infarct volumes (Bruce et al., 1996; Gary et al., 1998) and neuroprotection in ischemic stroke is mediated through the TNFR1-NFκB-FLIP(L)-ERK1/2 pathway (Taoufik et al., 2007; Lambertsen et al., 2009; Marques-Fernandez et al., 2013), downregulation of TNFR1 is likely to contribute to the lack of neuroprotection after TNF inhibition with etanercept (Gary et al., 1998; Lambertsen et al., 2009). The gene discussed is MAPK3; the disease is ischemic stroke.