Department of Neurosurgery, Boston Children's Hospital, Boston, MA 02115, USA.
F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA.
Int J Mol Sci. 2023 Oct 19;24(20):15359. doi: 10.3390/ijms242015359.
Although most pathways in the mature central nervous system cannot regenerate when injured, research beginning in the late 20th century has led to discoveries that may help reverse this situation. Here, we highlight research in recent years from our laboratory identifying oncomodulin (Ocm), stromal cell-derived factor (SDF)-1, and chemokine CCL5 as growth factors expressed by cells of the innate immune system that promote axon regeneration in the injured optic nerve and elsewhere in the central and peripheral nervous systems. We also review the role of ArmC10, a newly discovered Ocm receptor, in mediating many of these effects, and the synergy between inflammation-derived growth factors and complementary strategies to promote regeneration, including deleting genes encoding cell-intrinsic suppressors of axon growth, manipulating transcription factors that suppress or promote the expression of growth-related genes, and manipulating cell-extrinsic suppressors of axon growth. In some cases, combinatorial strategies have led to unprecedented levels of nerve regeneration. The identification of some similar mechanisms in human neurons offers hope that key discoveries made in animal models may eventually lead to treatments to improve outcomes after neurological damage in patients.
尽管成熟中枢神经系统中的大多数通路在受伤时都无法再生，但 20 世纪后期的研究发现可能有助于扭转这种情况。在这里，我们重点介绍了近年来我们实验室的研究成果，这些成果确定了基质细胞衍生因子 (SDF)-1 和趋化因子 CCL5 作为先天免疫系统细胞表达的生长因子，可促进损伤视神经以及中枢和周围神经系统中的其他部位的轴突再生。我们还回顾了新发现的 Ocm 受体 ArmC10 在介导许多这些作用中的作用，以及炎症衍生的生长因子与互补策略之间的协同作用，以促进再生，包括删除编码轴突生长内在抑制物的基因，操纵抑制或促进生长相关基因表达的转录因子，以及操纵轴突生长的细胞外抑制物。在某些情况下，组合策略导致了前所未有的神经再生水平。在人类神经元中发现一些类似的机制，为动物模型中的关键发现最终可能导致改善患者神经损伤后治疗结果提供了希望。
