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Science 310 (5745): 106-110

Copyright © 2005 by the American Association for the Advancement of Science

EGFR Activation Mediates Inhibition of Axon Regeneration by Myelin and Chondroitin Sulfate Proteoglycans

Vuk Koprivica,1 Kin-Sang Cho,2 Jong Bae Park,1 Glenn Yiu,1 Jasvinder Atwal,3 Bryan Gore,3 Jieun A. Kim,1 Estelle Lin,1 Marc Tessier-Lavigne,3 Dong Feng Chen,2 Zhigang He1*

Abstract: Inhibitory molecules associated with myelin and the glial scar limit axon regeneration in the adult central nervous system (CNS), but the underlying signaling mechanisms of regeneration inhibition are not fully understood. Here, we show that suppressing the kinase function of the epidermal growth factor receptor (EGFR) blocks the activities of both myelin inhibitors and chondroitin sulfate proteoglycans in inhibiting neurite outgrowth. In addition, regeneration inhibitors trigger the phosphorylation of EGFR in a calcium-dependent manner. Local administration of EGFR inhibitors promotes significant regeneration of injured optic nerve fibers, pointing to a promising therapeutic avenue for enhancing axon regeneration after CNS injury.

1 Division of Neuroscience, Children's Hospital, Boston, MA 02115, USA.
2 Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
3 Division of Research, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.

* To whom correspondence should be addressed. E-mail: zhigang.he{at}childrens.harvard.edu


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