A novel strategy to activate cytoprotective genes in the injured brain

► A strategy to increase cytoprotective gene expression in injured tissue is outlined. ► A peptide containing a DEETGE motif can increase Nrf2 responsive genes in vivo. ► Gene expression in injured brains requires a calpain cleavage site. ► This peptide decreases BBB compromise when infused pre- or post-brain injury. ► Cleavage sites for disease-specific proteases could be used to treat that condition.