title: A semaphorin 3A inhibitor blocks axonal chemorepulsion and enhances axon regeneration.
abstract: Secreted 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.
authors.affiliation: IRB Barcelona, Department of Cell Biology, University of Barcelona, and CIBERNED (ISCIII), Barcelona Science Park, Baldiri i Reixac 10, Barcelona E-08028, Spain.
authors.forename: Marisol
authors.initials: M
authors.lastname: Montolio
authors.forename: Joaquim
authors.initials: J
authors.lastname: Messeguer
authors.forename: Isabel
authors.initials: I
authors.lastname: Masip
authors.forename: Patricia
authors.initials: P
authors.lastname: Guijarro
authors.forename: Rosalina
authors.initials: R
authors.lastname: Gavin
authors.forename: José
authors.initials: J
authors.lastname: Antonio Del Río
authors.forename: Angel
authors.initials: A
authors.lastname: Messeguer
authors.forename: Eduardo
authors.initials: E
authors.lastname: Soriano
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D020439:Growth Cones; D051379:Mice; D009414:Nerve Growth Factors; D009416:Nerve Regeneration; D000075388:Netrin-1; D019151:Peptide Library; D010766:Phosphorylation; D012038:Regeneration; D040121:Semaphorin-3A / Q000037:antagonists & inhibitors*; D025521:Tumor Suppressor Proteins
chemical_list: D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D019151:Peptide Library; D040121:Semaphorin-3A; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; D038362:Glycogen Synthase Kinase 3