Fig. 6.

Model depicting a hypothetical mechanism by which growth arrest and DNA-damage-inducible protein 45 beta (Gadd45b) protects neurons against ischemic insults and activates its DNA methylation target brain-derived neurotrophic factor (BDNF). To compensate neuronal damages, global ischemic insults promote activation of Gadd45b and its binding to the promoter of BDNF exon IX. This, in turn, removes DNA methylation of cytosine residues at its promoter, allowing for activation of BDNF expression. Gadd45b can promote neuroprotective mechanisms in which indirectly inhibits Bax activation while increases Bcl-2 abundance. In consequence, the mitochondrial function is restored and it allows to block caspase activation.