Pasterkamp R Jeroen, Verhaagen Joost
Department of Pharmacology and Anatomy, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
Philos Trans R Soc Lond B Biol Sci. 2006 Sep 29;361(1473):1499-511. doi: 10.1098/rstb.2006.1892.
Semaphorins are developmental axon guidance cues that continue to be expressed during adulthood and are regulated by neural injury. During the formation of the nervous system, repulsive semaphorins guide axons to their targets by restricting and channelling their growth. They affect the growth cone cytoskeleton through interactions with receptor complexes that are linked to a complicated intracellular signal transduction network. Following injury, regenerating axons stop growing when they reach the border of the glial-fibrotic scar, in part because they encounter a potent molecular barrier that inhibits growth cone extension. A number of secreted semaphorins are expressed in the glial-fibrotic scar and at least one transmembrane semaphorin is upregulated in oligodendrocytes surrounding the lesion site. Semaphorin receptors, and many of the signal transduction components required for semaphorin signalling, are present in injured central nervous system neurons. Here, we review evidence that supports a critical role for semaphorin signalling in axon regeneration, and highlight a number of challenges that lie ahead with respect to advancing our understanding of semaphorin function in the normal and injured adult nervous system.
信号素是发育过程中的轴突导向因子，在成年期持续表达，并受神经损伤调节。在神经系统形成过程中，排斥性信号素通过限制和引导轴突生长，将其导向目标。它们通过与连接到复杂细胞内信号转导网络的受体复合物相互作用，影响生长锥细胞骨架。损伤后，再生轴突到达胶质纤维化瘢痕边界时停止生长，部分原因是它们遇到了抑制生长锥延伸的强大分子屏障。一些分泌型信号素在胶质纤维化瘢痕中表达，并且至少有一种跨膜信号素在损伤部位周围的少突胶质细胞中上调。信号素受体以及信号素信号传导所需的许多信号转导成分，存在于受损的中枢神经系统神经元中。在这里，我们综述了支持信号素信号传导在轴突再生中起关键作用的证据，并强调了在推进我们对正常和受损成年神经系统中信号素功能的理解方面，仍面临的一些挑战。
