Chemistry & Biology
Volume 16, Issue 7, 31 July 2009, Pages 691-701
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Article
A Semaphorin 3A Inhibitor Blocks Axonal Chemorepulsion and Enhances Axon Regeneration

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Summary

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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Cited by (0)

3

Present address: Department of Physiological Sciences II, Faculty of Medicine, Bellvitge Campus, University of Barcelona, Barcelona, Spain

4

Present address: Laboratory of Neural Circuit Development, Institute of Neuroscience (ION), Chinese Academy of Sciences, Shanghai, China

5

Present address: Institut de Bioenginyeria de Catalunya (IBEC), Parc Científic de Barcelona, Barcelona, Spain