The present invention is directed to novel tissue protective peptides. Thetissue protective peptides of the invention may bind to a tissue protectivereceptor complex. In particular, the present invention is drawn to tissueprotective peptides derived from or sharing consensus sequences with portionsof cytokine receptor ligands, including Erythropoietin (EPO), that are notinvolved in the binding of the ligand to the receptor complex, e.g., to theEPO receptor homodimer. Accordingly, the tissue protective peptides of theinvention are derived from the amino acid sequences of regions of cytokinereceptor ligands that are generally located on or within the region of theligand protein that is opposite of the receptor complex, i.e., are generallyderived from amino acid sequences of regions of the ligand protein that faceaway from the receptor complex while the ligand is bound to the receptor. Theinvention is further directed to the consensus sequences for use inengineering a synthetic tissue protective peptide. These tissue protectivepeptides also include fragments, chimeras, as well as peptides designed tomimic the spatial localization of key amino acid residues within the tissueprotective receptor ligands, e.g., EPO. The invention further encompassesmethods for treating or preventing a disease or disorder using tissueprotective peptides of the current invention. The invention also encompassesmethods for enhancing excitable tissue function using tissue protectivepeptides of the current invention.
