Mount Sinai Researchers Identify Aryl Hydrocarbon Receptor as Molecular "Brake" Preventing Spinal Cord Regeneration

Mount Sinai researchers find that blocking the AHR protein can restart axonal growth and restore function after spinal cord and nerve injuries.

By: AXL Media

Published: Apr 1, 2026, 11:12 AM EDT

Source: Information for this report was sourced from The Mount Sinai Hospital / Mount Sinai School of Medicine

Decoding the Limitation of Neural Repair in Mammals

The inability of the adult mammalian nervous system to repair itself after significant trauma has long been a primary obstacle in neurology. When axons—the long, thread-like extensions of neurons that transmit electrical impulses—are severed due to spinal cord or peripheral nerve injuries, the resulting loss of sensation or movement is often permanent. A new study published in the journal Nature by researchers at Mount Sinai identifies a specific molecular mechanism responsible for this restricted repair process. The team found that neurons possess an internal regulatory system that forcedly balances the immediate need to cope with cellular stress against the long-term goal of regenerating damaged fibers.

The Aryl Hydrocarbon Receptor as a Metabolic Switch

At the center of this discovery is the aryl hydrocarbon receptor (AHR), a protein historically known for sensing environmental toxins and pollutants. The research team, led by Dr. Hongyan Zou, discovered that AHR serves a previously unknown role as a "molecular brake" within the nervous system. Following an injury, AHR signaling becomes highly active, shifting the neuron’s metabolic resources away from growth and toward a state of defensive maintenance. While this response is intended to protect the cell from the immediate trauma of the injury, it effectively halts the production of new proteins required to extend axonal fibers across a wound site.

Shifting the Balance From Survival to Regeneration

The study utilized mouse models to demonstrate that inhibiting AHR can fundamentally change a neuron's post-injury strategy. When researchers used drugs or genetic engineering to remove AHR, the "brake" was released, allowing neurons to enter a regenerative state. Instead of focusing solely on protein quality control and stress management—a process known as proteostasis—the AHR-deficient neurons began producing the structural proteins necessary for building new axonal connections. This shift resulted in a measurable improvement in both motor and sensory recovery, suggesting that the drive to regenerate can be artificially induced even in adult tissue.