In addition to mTOR, several other downstream effectors of the PI3K/Akt signaling pathway including GSK3β, MDM2, and NF-κB have been reported to be activated by treatment of recombinant hMANF in the rodent brain, which was associated with enhanced neuron survival in neurodegenerative diseases and intracerebral hemorrhage models (Hao et al., 2017; Zhang et al., 2017b; Li et al., 2018; Xu M. et al., 2018). This evidence concerns the gene MDM2 and intracerebral hemorrhage.