Coupe David, Bossing Torsten
Peninsula Medical School, University of Plymouth, John Bull Building, 16 Research Way, Plymouth PL6 8BU, U.K.
Neuronal Signal. 2022 Apr 13;6(1):NS20210051. doi: 10.1042/NS20210051. eCollection 2022 Apr.
Millions of people experience injury to the central nervous system (CNS) each year, many of whom are left permanently disabled, providing a challenging hurdle for the field of regenerative medicine. Repair of damage in the CNS occurs through a concerted effort of phagocytosis of debris, cell proliferation and differentiation to produce new neurons and glia, distal axon/dendrite degeneration, proximal axon/dendrite regeneration and axon re-enwrapment. In humans, regeneration is observed within the peripheral nervous system, while in the CNS injured axons exhibit limited ability to regenerate. This has also been described for the fruit fly . Powerful genetic tools available in have allowed the response to CNS insults to be probed and novel regulators with mammalian orthologs identified. The conservation of many regenerative pathways, despite considerable evolutionary separation, stresses that these signals are principal regulators and may serve as potential therapeutic targets. Here, we highlight the role of CNS injury models in providing key insight into regenerative processes by exploring the underlying pathways that control glial and neuronal activation in response to insult, and their contribution to damage repair in the CNS.
每年有数百万人遭受中枢神经系统(CNS)损伤,其中许多人会永久性残疾,这给再生医学领域带来了具有挑战性的障碍。中枢神经系统损伤的修复是通过清除碎片的吞噬作用、细胞增殖和分化以产生新的神经元和神经胶质细胞、远端轴突/树突退化、近端轴突/树突再生以及轴突重新包裹等协同作用来实现的。在人类中,外周神经系统内可观察到再生,而在中枢神经系统中,受损轴突的再生能力有限。果蝇也有类似情况。果蝇所具备的强大遗传工具使得对中枢神经系统损伤的反应得以探究,并鉴定出了具有哺乳动物直系同源物的新型调节因子。尽管进化上有很大差异,但许多再生途径的保守性强调了这些信号是主要调节因子,可能成为潜在的治疗靶点。在这里,我们通过探索控制神经胶质细胞和神经元对损伤作出反应时激活的潜在途径及其对中枢神经系统损伤修复的贡献,来突出中枢神经系统损伤模型在深入了解再生过程中的作用。