AhR抑制通过应激-生长开关促进轴突再生，这一成果由美国西奈山伊坎医学院Hongyan Zou团队经过不懈努力而取得。该研究于2026年4月1日发表于国际一流学术期刊《自然》杂志上。

本研究发现芳烃受体（AhR）是一种配体激活的碱性螺旋-环-螺旋/PER-ARNT-SIM （bHLH-PAS）转录因子，是这种应激生长开关的关键调节因子。课题组研究人员发现，在周围神经和脊髓损伤模型中，配体介导的AhR信号传导抑制轴突生长，而神经元缺失或AhR的药理抑制促进轴突再生和功能恢复。机制研究表明，腋切开术诱导的AhR激活在背根神经节神经元中加强蛋白质平衡和应激反应程序，以保持组织完整性。相比之下，AhR消融可将神经元反应重定向到提高新生翻译和促生长信号，从而使轴突再生。这种促进生长的作用需要HIF1α，具有丰富的代谢和再生途径的共享转录靶点。单细胞和表观基因组分析进一步揭示，AhR调控参与综合应激反应和DNA羟甲基化，以重新连接神经元损伤反应程序。总之，他们的研究结果证实AhR是轴突再生的神经元制动器，整合环境感知、蛋白质稳态和代谢信号来控制应激适应和轴突修复之间的平衡。

研究人员表示，哺乳动物中枢神经系统的轴突再生是有限的。神经元在轴突损伤后会平衡应激反应和再生需求，但其机制尚不清楚。

附：英文原文

Title: AhR inhibition promotes axon regeneration via a stress–growth switch

Author: Halawani, Dalia, Wang, Yiqun, Li, Jiaxi, Halperin, Daniel, Ni, Haofei, Estill, Molly, Ramakrishnan, Aarthi, Shen, Li, Sefiani, Arthur, Geoffroy, Cdric G., Friedel, Roland H., Zou, Hongyan

Issue&Volume: 2026-04-01

Abstract: Axon regeneration is limited in the mammalian central nervous system1. Neurons must balance stress responses with regenerative demands after axonal injury2, but the mechanisms remain unclear. Here we identify aryl hydrocarbon receptor (AhR), a ligand-activated basic helix–loop–helix/PER-ARNT-SIM (bHLH-PAS) transcription factor, as a key regulator of this stress–growth switch. We show that ligand-mediated AhR signalling restrains axon growth, whereas neuronal deletion or pharmacological inhibition of AhR promotes axonal regeneration and functional recovery in both peripheral nerve and spinal cord injury models. Mechanistic studies reveal that axotomy-induced AhR activation in dorsal root ganglion neurons enforces proteostasis and stress-response programs to preserve tissue integrity. By contrast, AhR ablation redirects the neuronal response towards elevated de novo translation and pro-growth signalling, enabling axon regeneration. This growth-promoting effect requires HIF1α, with shared transcriptional targets enriched for metabolic and regenerative pathways. Single-cell and epigenomic analyses further revealed that the AhR regulon engages the integrated stress response and DNA hydroxymethylation to rewire neuronal injury-response programs. Together, our findings establish AhR as a neuronal brake on axon regeneration, integrating environmental sensing, protein homeostasis and metabolic signalling to control the balance between stress adaptation and axonal repair.

DOI: 10.1038/s41586-026-10295-z

Source: https://www.nature.com/articles/s41586-026-10295-z