Researchers at the Icahn School of Medicine at Mount Sinai announced on Apr. 1 that they have identified a molecular switch in neurons that restricts the regrowth of damaged axonal fibers. The study, published in Nature, suggests that blocking a protein known as the aryl hydrocarbon receptor (AHR) could help promote neural regeneration and restore function following injuries to peripheral nerves or the spinal cord.
The discovery addresses a long-standing question about why adult mammalian neurons struggle to repair themselves after injury. Axons are long fibers essential for communication between nerve cells, and their ability to regrow is critical for recovery from nervous system injuries. However, most injuries result in limited or no recovery due to poor axonal regeneration.
The research team found that AHR acts as a key regulator in determining how neurons respond after being injured. “When neurons are injured, they must deal with stress while also trying to regrow their axons,” said Hongyan Zou, MD, PhD, Professor of Neurosurgery and Neuroscience at Icahn School of Medicine at Mount Sinai and senior author of the study. “We discovered that AHR functions like a brake that shifts neurons toward managing stress rather than rebuilding damaged connections.” When AHR signaling was blocked or removed from neurons in mouse models, there was improved regrowth of axonal fibers and better recovery of motor and sensory function.
Further experiments revealed that AHR helps protect injured neurons by maintaining protein quality control—a process called proteostasis—but this protective response reduces new protein production needed for growth. Turning off AHR led to increased production of new proteins and activation of pathways supporting axon regeneration. The researchers also found this regenerative response depends on another factor called HIF-1α involved in metabolism and tissue repair.
“This discovery shows that neurons use AHR to balance survival and regeneration,” Zou said. “By releasing this brake, we can push neurons into a state that favors repair.” Originally known as an environmental toxin sensor, AHR now appears to play an unexpected role inside nerve cells by linking environmental sensing with regenerative capacity after injury.
Although several drugs targeting AHR are already being tested for other diseases, more research is required before applying these findings clinically for nerve or spinal cord injuries. Future studies will focus on evaluating different types of neural damage and optimizing treatment strategies using gene therapy or drug-based approaches aimed at reducing neuronal AHR activity.
