Updates and challenges of axon regeneration in the mammalian central nervous system.
Updates and challenges of axon regeneration in the mammalian central nervous system.
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哺乳动物中枢神经系统轴突再生的研究进展与挑战。
DOI：
10.1093/jmcb/mjaa026
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发表时间：
2020-10-01
影响因子：
5.5
通讯作者：
Zhou FQ
中科院分区：
文献类型：
--
作者：
Qian C;Zhou FQ
哺乳动物中枢神经系统（CNS）的轴突再生一直是一个长期存在且极具挑战性的问题。成功的CNS轴突再生将有益于许多涉及轴突损伤的人类疾病，如脊髓损伤、创伤性脑损伤、青光眼和神经退行性疾病。目前的共识是，在成熟的中枢神经系统神经元的内在再生能力下降和存在的外源性抑制剂阻断轴突再生的轴突再生的两个主要障碍。在过去的十年中，通过调控基因转录来靶向内源性轴突生长能力的研究在视神经和/或脊髓再生中产生了非常有希望的结果。各种信号通路或核转录因子的直接操作已被证明足以驱动CNS轴突再生。汇聚的证据表明，一些促再生转录组状态，这通常是由更全面的表观遗传调控完成，存在协调损伤传感和轴突再生的复杂任务。此外，通过转录组和表观基因组修饰实现的遗传重编程为增强轴突再生提供了新的机制。最近的研究也强调了重塑神经细胞骨架在克服外源性抑制信号中的重要作用。然而，我们对神经元调节其内在轴突再生能力和对外在抑制性信号反应的细胞和分子机制的认识仍然是支离破碎的。在这里，我们提供了最新的研究进展，轴突再生和长距离轴突再生和随后的功能恢复的主要挑战进行了讨论。
Axon regeneration in the mammalian central nervous system (CNS) has been a long-standing and highly challenging issue. Successful CNS axon regeneration will benefit many human diseases involving axonal damage, such as spinal cord injury, traumatic brain injury, glaucoma, and neurodegenerative diseases. The current consensus is that the diminished intrinsic regenerative ability in mature CNS neurons and the presence of extrinsic inhibitors blocking axon regrowth are two major barriers for axon regeneration. During the past decade, studies targeting the intrinsic axon growth ability via regulation of gene transcription have produced very promising results in optic nerve and/or spinal cord regeneration. Manipulations of various signaling pathways or the nuclear transcription factors directly have been shown to sufficiently drive CNS axon regrowth. Converging evidence reveals that some pro-regenerative transcriptomic states, which are commonly accomplished by more comprehensive epigenetic regulations, exist to orchestrate the complex tasks of injury sensing and axon regeneration. Moreover, genetic reprogramming achieved via transcriptome and epigenome modifications provides novel mechanisms for enhancing axon regeneration. Recent studies also highlighted the important roles of remodeling neuronal cytoskeleton in overcoming the extrinsic inhibitory cues. However, our knowledge about the cellular and molecular mechanisms by which neurons regulate their intrinsic axon regeneration ability and response to extrinsic inhibitory cues is still fragmented. Here, we provide an update about recent research progress in axon regeneration and discuss major remaining challenges for long-distance axon regeneration and the subsequent functional recovery.
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