Publication Date:
2005-10-08
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koprivica, Vuk -- Cho, Kin-Sang -- Park, Jong Bae -- Yiu, Glenn -- Atwal, Jasvinder -- Gore, Bryan -- Kim, Jieun A -- Lin, Estelle -- Tessier-Lavigne, Marc -- Chen, Dong Feng -- He, Zhigang -- New York, N.Y. -- Science. 2005 Oct 7;310(5745):106-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Neuroscience, Children's Hospital, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16210539" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Axons/drug effects/*physiology
;
Calcium/metabolism
;
Cells, Cultured
;
Chondroitin Sulfate Proteoglycans/*metabolism
;
Enzyme Inhibitors/pharmacology
;
Erlotinib Hydrochloride
;
GPI-Linked Proteins
;
Humans
;
Mice
;
Myelin Proteins/*metabolism/pharmacology
;
Nerve Crush
;
*Nerve Regeneration/drug effects
;
Neurites/drug effects/physiology
;
Optic Nerve/drug effects/physiology
;
Optic Nerve Injuries/drug therapy
;
Phosphorylation
;
Quinazolines/pharmacology
;
Receptor, Epidermal Growth Factor/*antagonists & inhibitors/*metabolism
;
Receptors, Cell Surface/metabolism
;
Retinal Ganglion Cells/drug effects/physiology
;
Signal Transduction/drug effects
;
Tyrphostins/pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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