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. 2009 Jul 31;16(7):691-701.
doi: 10.1016/j.chembiol.2009.05.006. Epub 2009 Jul 16.

A semaphorin 3A inhibitor blocks axonal chemorepulsion and enhances axon regeneration

Marisol Montolio  1 , Joaquim Messeguer, Isabel Masip, Patricia Guijarro, Rosalina Gavin, José Antonio Del Río, Angel Messeguer, Eduardo Soriano
Affiliations

A semaphorin 3A inhibitor blocks axonal chemorepulsion and enhances axon regeneration

Marisol Montolio et al. Chem Biol. .

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.

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