MANF and Cerebral ischemia: We conclude that the C-terminal KDEL-like motif, which is critical for the intracellular neuroprotection by MANF in SCG neurons, is not required for its neuroprotective activity when applied extracellularly in vivo, at least in the model of cerebral ischemia, whereas the intact CXXC motif is critical in both modes of action of MANF.