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A Semaphorin 3A Inhibitor Blocks Axonal Chemorepulsion and Enhances Axon Regeneration

AuthorsMontolio, Marisol; Messeguer, Joaquim; Masip, Isabel ; Guijarro, Patricia; Gavin, Rosalina; Río, José Antonio del; Messeguer Peypoch, Ángel ; Soriano, Eduardo
Axon guidance
Semaphorin Induced Chemorepulsion Inhibitor (SICHI)
Peripheral nervous system and central nervous system injury
Issue Date16-Jul-2009
CitationChemistry and Biology (2009), doi: 10.1016/j.chembiol.2009.05.006 (In press)
AbstractSecreted semaphorins are a large group of extracellular proteins involved in a variety of processes during development, including neuronal migration and axon guidance. We screened a peptoid combinatorial library to search for semaphorin 3A inhibitors, and identified a peptoid (SICHI: semaphorin Induced chemorepulsion inhibitor) that blocks semaphorin 3A-chemorepulsion and growth-cone collapse in axons at millimolar concentrations. SICHI inhibits the binding of semaphorin 3A to its receptor complex (neuropilin 1/plexin A1) and semaphorin 3A-induced phosphorylation of GSK3. Chemorepulsion induced by semaphorin 3F or netrin 1 is not blocked by SICHI. We also show that SICHI promotes neural regeneration of damaged axons. We suggest that SICHI, a selective inhibitor of semaphorin 3A, is of therapeutic interest for approaches aimed at promoting axonal regeneration and brain repair.
Description11 pages, 7 figures.-- Article in press.
Supporting information (Suppl. discussion, suppl. experimental procedures + suppl. fogis S1-S3, 5 pages) available at: http://dx.doi.org/10.1016/j.chembiol.2009.05.006
Publisher version (URL)http://dx.doi.org/10.1016/j.chembiol.2009.05.006
Appears in Collections:(IQAC) Artículos
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