A Semaphorin 3A Inhibitor Blocks Axonal Chemorepulsion and Enhances Axon Regeneration
A Semaphorin 3A Inhibitor Blocks Axonal Chemorepulsion and Enhances Axon Regeneration
复制标题
DOI：
10.1016/j.chembiol.2009.05.006
复制
发表时间：
2009-07-31
影响因子：
--
通讯作者：
Soriano, Eduardo
中科院分区：
文献类型：
--
作者：
Montolio, Marisol;Messeguer, Joaquim;Soriano, Eduardo
分泌型信号蛋白是一大类细胞外蛋白质，参与发育过程中的各种过程，包括神经元迁移和轴突导向。我们筛选了一个类肽组合库，以寻找脑信号蛋白3A抑制剂，并确定了一个类肽（SICHI：脑信号蛋白诱导的化学排斥抑制剂），阻止脑信号蛋白3A-化学排斥和生长锥崩溃的轴突在毫摩尔浓度。SICHI抑制脑信号蛋白3A与其受体复合物（神经纤毛蛋白1/丛蛋白A1）的结合和脑信号蛋白3A诱导的GSK 3磷酸化。由semaphorin 3F或netrin 1诱导的化学排斥不被SICHI阻断。我们还表明，SICHI促进受损轴突的神经再生。我们认为，SICHI，一种选择性抑制剂semaphorin 3A，是治疗的兴趣，旨在促进轴突再生和脑修复的方法。
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.