生物谷报道：Johns Hopkins大学的研究人员已经发现了硫酸软骨素蛋白质家族阻止生长着的神经并使它们在发育过程中走“正途”的机制。这一发现为人类克服这种蛋白质在发育完成后阻止受损神经再生提供了一个机会。
硫酸软骨素（CSPGs），它通过集合其它蛋白和因子来阻止损伤后的神经再生，但是在这些分子中究竟是哪些物质阻止神经的再生就不得而知了。
在对发育期的大鼠神经生长进行研究时，Hopkins的教授发现了CSPGs的no-growth effects与一种叫做semaphorin 5A蛋白之间的联系。他们发现当CSPGs与semaphorin 5A结合时，生长中的神经就被中止，而抑制这种特殊的反应就能使神经继续生长。
当一个神经受损时，大量的CSPG蛋白就会积累到受伤位点上。这些蛋白接着引来一系列其它因子，其中就包括semaphorins。实验表明没有CSPGs，受损的神经能够在培养皿中再生。因此，这一发现暗示抑制CSPGs或许能在动物中达到同样的效果。在实验室中，Kantor模拟了正在发育的大鼠的大脑发育中的一个特殊步骤。在这个步骤中，特定的神经开始将最终会形成大脑两个部分的区域连接起来。
Figure 1. Sema5A Is Important for the Proper Development of the Fasciculus Retroflexus(A) Schematic lateral view of the developing rat diencephalon showing that the fasciculus retroflexus (FR) originates in the habenula (Hb) nucleus and extends between prosomere 1 (pros1) and prosomere 2 (pros2). Prosomere 1 expresses the repellent Sema3F, while prosomere 2 expresses an unknown membrane-attached repellent activity.(B) Horizontal brain section showing that Sema5A transcript is found in the Hb nucleus (open arrowheads).(C) Axons extending from E15.5 Hb explants are strongly labeled by Sema5A antibodies.(D and E) Sagittal (D) and horizontal (E) brain sections show that Sema5A transcript is expressed in prosomere 2 (filled arrowheads) adjacent to the FR (open arrowheads).(F) The alkaline phosphatase tagged ecto-domain of Sema5A (AP-5Aecto) binds both to FR axons (open arrowheads) and to prosomere 2 (outlined area).(G–I) E13.5 rat organotypic diencephalon explants stained with antibodies against TAG-1. Compared to explants treated with control IgG (G), explants treated with Sema5A function-blocking antibodies (5A) (H) show significantly more FR fibers (open arrowhead) crossing inappropriately into prosomere 2 (I). Results are expressed as the mean number of fibers per explant crossing into prosomere 2 ± SEM.(J) The width of the MTT (closed arrowhead) was not significantly different between 5A and IgG treatments. Results are expressed as the mean width of the MTT (in m) ± SEM. The letters in the graph legends correspond to the letters in the panels. DIV, days in vitro. *p < 0.001, Student's t test. All scale bars equal 100 m.
Figure 2. Sema5A Expressed in HEK 293 Cells Is a Permissive Substrate for Hb Axons(A–E) Structure/function analysis of Sema5A. Compared to membranes collected from HEK 293 cells transfected with GFP (A), membranes from full-length Sema5A (FL-5A) transfected cells (B) are a permissive substrate for Hb axons. (C) The permissive effects of Sema5A localize to the thrombospondin repeats. While the sema domain alone (D) has no effect on Hb axons, when oligomerized with the cartilage oligomeric matrix protein (COMP) assembly domain (E), the sema domain becomes an inhibitory cue for Hb axons. For all membrane stripe assays in this study, the horizontal boxes at the top of each assay indicate the composition of experimental and control stripes, with the experimental stripe designated by the left-most box.(F) Constructs used in this study. The purple circles represent alkaline phosphatase (AP).(G) Quantification of data in (A)–(E). The scale bar equals 100 m.
由于这些神经的精确延伸需要semaphorin 5A，因此Kantor能够确定与之反应的关键分子。最终，他发现CSPGs通过与semaphorin 5A结合来阻止神经穿过神经被模拟区域到达靶标。通过添加一种只能摧毁CSPGs的酶来阻止这种反应，研究人员能够让神经穿透这个空间。
Kantor还发现semaphorin 5A能够使生长的神经束聚集在一起。其它semaphorins既能鼓励神经生长又能抑制它的生长。Semaphorin的这种双向功能可能源于它和其它分子的相互作用，但目前还不知道具体是什么分子
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