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

被引：55

作者：

Montolio, Marisol ^{[1
,2
]}

Messeguer, Joaquim ^{[3
]}

Masip, Isabel ^{[3
]}

Guijarro, Patricia ^{[1
,2
]}

Gavin, Rosalina ^{[1
,2
]}

Antonio del Rio, Jose ^{[1
,2
]}

Messeguer, Angel ^{[3
]}

Soriano, Eduardo ^{[1
,2
]}

机构：

[1] Univ Barcelona, Dept Cell Biol, IRB Barcelona, E-08028 Barcelona, Spain

[2] CIBERNED ISCIII, E-08028 Barcelona, Spain

[3] AQAC CSIC, Dept Biol Organ Chem, E-08034 Barcelona, Spain

来源：

CHEMISTRY & BIOLOGY | 2009年 / 16卷 / 07期

关键词：

GROWTH CONE COLLAPSE; CHICK NERVOUS-SYSTEM; CAJAL-RETZIUS CELLS; SPINAL-CORD INJURY; IN-VIVO; SECRETED SEMAPHORINS; NOGO RECEPTOR; EXTRACELLULAR DOMAIN; FUNCTIONAL RECOVERY; GUIDANCE MOLECULES;

D O I：

10.1016/j.chembiol.2009.05.006

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：691 / 701

页数：11

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