The intracellular prosurvival activity and subcellular localization of the mutants were studied in the models of apoptotic primary SCG and DRG neurons, the former being currently the best-characterized model to study neuronal survival.26, 27, 28 As MANF also protects the neurons when injected into the extracellular space of the brain tissue, for example, on the model of cerebral ischemia,9, 10 we studied the prosurvival activity of MANF mutants on that model as well. Here, MANF is linked to Cerebral ischemia.