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一种信号素3A抑制剂可阻断轴突化学排斥并增强轴突再生。

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

作者信息

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

机构信息

IRB Barcelona, Department of Cell Biology, University of Barcelona, and CIBERNED (ISCIII), Barcelona Science Park, Baldiri i Reixac 10, Barcelona E-08028, Spain.

出版信息

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

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.

摘要

分泌型信号素是一大类细胞外蛋白,参与发育过程中的多种进程,包括神经元迁移和轴突导向。我们筛选了一个类肽组合文库以寻找信号素3A抑制剂,并鉴定出一种类肽(SICHI:信号素诱导化学排斥抑制剂),它在毫摩尔浓度下可阻断轴突中信号素3A诱导的化学排斥和生长锥塌陷。SICHI抑制信号素3A与其受体复合物(神经纤毛蛋白1/丛状蛋白A1)的结合以及信号素3A诱导的GSK3磷酸化。信号素3F或网蛋白1诱导的化学排斥不受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作为信号素3A的选择性抑制剂,对于旨在促进轴突再生和脑修复的方法具有治疗意义。

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