成人外周神经元,与成人中枢神经元相比,轴突损伤后能够再生。很多注意力集中在两个地方伴随这种再生的变化上,远端神经段(轴突碎片的吞噬作用,施万细胞表面性质的变化,和诱导生长因子和细胞因子的发生)和神经元细胞体(细胞形态和基因表达发生急剧变化)。轴突化细胞体的变化通常被称为“细胞体反应”。“当前综述的重点是细胞因子家族,糖蛋白130(gp130)细胞因子,它们通过常见的gp130信号受体产生作用,并作为轴突切除的外周神经元的损伤信号,触发基因表达和神经突生长的变化。这些细胞因子在交感神经的反应中起重要作用,感官,和运动神经元受伤。在这种情况下,这些细胞因子的最佳研究是白血病抑制因子(LIF)和白细胞介素(IL)-6,但对条件gp130基因敲除动物的实验表明,该家族的其他成员,尚未确定,也参与其中。主要的gp130信号通路是Janus激酶(JAK)的激活和转录因子信号转导和转录激活因子(STAT),尽管其他下游途径如丝裂原活化蛋白激酶(MAPK)/细胞外信号调节激酶(ERK)也可能发挥作用。gp130信号传导可能涉及旁分泌,逆行,和这些细胞因子的自分泌作用。最近的研究表明,操纵这种细胞因子系统也可以刺激受损的中枢神经元再生。
Adult peripheral neurons, in contrast to adult central neurons, are capable of regeneration after axonal damage. Much attention has focused on the changes that accompany this regeneration in two places, the distal nerve segment (where phagocytosis of axonal debris, changes in the surface properties of Schwann cells, and induction of growth factors and cytokines occur) and the neuronal cell body (where dramatic changes in cell morphology and gene expression occur). The changes in the axotomized cell body are often referred to as the \"cell body response.\" The focus of the current review is a family of cytokines, the glycoprotein 130 (gp130) cytokines, which produce their actions through a common gp130 signaling receptor and which function as injury signals for axotomized peripheral neurons, triggering changes in gene expression and in neurite outgrowth. These cytokines play important roles in the responses of sympathetic, sensory, and motor neurons to injury. The best studied of these cytokines in this context are leukemia inhibitory factor (LIF) and interleukin (IL)-6, but experiments with conditional gp130 knockout animals suggest that other members of this family, not yet determined, are also involved. The primary gp130 signaling pathway shown to be involved is the activation of Janus kinase (JAK) and the transcription factors Signal Transducers and Activators of Transcription (STAT), though other downstream pathways such as mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) may also play a role. gp130 signaling may involve paracrine, retrograde, and autocrine actions of these cytokines. Recent studies suggest that manipulation of this cytokine system can also stimulate regeneration by injured central neurons.