MANF can inhibit apoptosis/necrosis in the ischemic brain (Airavaara et al., 2009; Yang et al., 2014), and the CxxC-motif is indispensable for the neuroprotective effect of MANF in ischemic stroke, possibly because of its importance in maintaining MANF’s structural conformation (Matlik et al., 2015). This evidence concerns the gene MANF and ischemic stroke.