Provided herein are tissue protective peptides derived from or sharing consensus sequences with portions of cytokine receptor ligands, including Erythropoietin (EPO), that are generally located on or within the region of the cytokine receptor ligand that faces away from a receptor complex while the ligand is bound to the receptor. Also provide herein are fragments, chimeras, as well as peptides designed to mimic the spatial localization of key amino acid residues within the tissue protective receptor ligands, e.g., EPO； methods for treating or preventing a disease or disorder using tissue protective peptides； and methods for enhancing excitable tissue function using tissue protective peptides.
