Modifying Erythropoietin Activity

Science's STKE  13 Jul 2004:
Vol. 2004, Issue 241, pp. tw255
DOI: 10.1126/stke.2412004tw255

The cytokine erythropoietin binds to the classic erythropoietin receptor to mediate hematopoiesis and has independent tissue-protective bioactivities. Leist et al. (see the Perspective by Ehrenreich) generated a distinct isoform of erythropoietin that separates its two activities. A carbamoylated derivative did not bind to the classical erythropoietin receptor and lost the hematopoietic capacity of natural erythropoietin. However, the derivative was neuroprotective in animal models of stroke, spinal cord injury, experimental autoimmune encephalomyelitis, and diabetic neuropathy.

M. Leist, P. Ghezzi, G. Grasso, R. Bianchi, P. Villa, M. Fratelli, C. Savino, M. Bianchi, J. Nielsen, J. Gerwien, P. Kallunki, A. K. Larsen, L. Helboe, S. Christensen, L. O. Pedersen, M. Nielsen, L. Torup, T. Sager, A. Sfacteria, S. Erbayraktar, Z. Erbayraktar, N. Gokmen, O. Yilmaz, C. Cerami-Hand, Q. Xie, T. Coleman, A. Cerami, M. Brines, Derivatives of erythropoietin that are tissue protective but not erythropoietic. Science 305, 239-242 (2004). [Abstract] [Full Text]

H. Ehrenreich, A boost for translational neuroscience. Science 305, 184-185 (2004). [Summary] [Full Text]