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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Axons / drug effects
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Axons / physiology*
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Calcium / metabolism
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Cells, Cultured
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Chondroitin Sulfate Proteoglycans / metabolism*
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Enzyme Inhibitors / pharmacology
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ErbB Receptors / antagonists & inhibitors*
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ErbB Receptors / metabolism*
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Erlotinib Hydrochloride
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GPI-Linked Proteins
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Humans
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Mice
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Myelin Proteins / metabolism*
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Myelin Proteins / pharmacology
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Nerve Crush
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Nerve Regeneration* / drug effects
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Neurites / drug effects
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Neurites / physiology
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Nogo Proteins
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Nogo Receptor 1
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Optic Nerve / drug effects
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Optic Nerve / physiology
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Optic Nerve Injuries / drug therapy
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Phosphorylation
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Quinazolines / pharmacology
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Receptors, Cell Surface / metabolism
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Retinal Ganglion Cells / drug effects
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Retinal Ganglion Cells / physiology
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Signal Transduction / drug effects
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Tyrphostins / pharmacology
Substances
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Chondroitin Sulfate Proteoglycans
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Enzyme Inhibitors
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GPI-Linked Proteins
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Myelin Proteins
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Nogo Proteins
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Nogo Receptor 1
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Quinazolines
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RTN4 protein, human
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Receptors, Cell Surface
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Rtn4 protein, mouse
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Rtn4r protein, mouse
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Tyrphostins
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RTKI cpd
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Erlotinib Hydrochloride
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ErbB Receptors
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Calcium