1. A Semaphorin 3A Inhibitor Blocks Axonal Chemorepulsion and Enhances Axon Regeneration
- Author
-
Montolio, Marisol, Messeguer, Joaquim, Masip, Isabel, Guijarro, Patricia, Gavin, Rosalina, Río, José Antonio del, Messeguer Peypoch, Ángel, Soriano, Eduardo, Montolio, Marisol, Messeguer, Joaquim, Masip, Isabel, Guijarro, Patricia, Gavin, Rosalina, Río, José Antonio del, Messeguer Peypoch, Ángel, and Soriano, Eduardo
- 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.
- Published
- 2009