The present invention is directed to novel tissue protective peptides. The tissue protective peptides of the invention may bind to a tissue protective 
receptor complex. In particular, the present invention is drawn to tissue protective peptides derived from or sharing 
consensus sequences with portions of 
cytokine receptor ligands, including 
Erythropoietin (EPO), that are not involved in the binding of the ligand to the 
receptor complex, e.g., to the EPO receptor homodimer. Accordingly, the tissue protective peptides of the invention are derived from the 
amino acid sequences of regions of 
cytokine receptor ligands that are generally located on or within the region of the ligand 
protein that is opposite of the 
receptor complex, i.e., are generally derived from 
amino acid sequences of regions of the ligand 
protein that face away from the 
receptor complex while the ligand is bound to the receptor. The invention is further directed to the 
consensus sequences for use in 
engineering a synthetic tissue protective 
peptide. These tissue protective peptides also include 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. The invention further encompasses methods for treating or preventing a 
disease or disorder using tissue protective peptides of the current invention. The invention also encompasses methods for enhancing excitable tissue function using tissue protective peptides of the current invention.