Researchers at the Icahn School of Medicine at Mount Sinai have identified the aryl hydrocarbon receptor (AHR) as a molecular mechanism that restricts the ability of injured neurons to regrow damaged axons, as reported in a study published in the journal Nature. The study suggests that blocking AHR could promote nerve regeneration and improve recovery following damage to peripheral nerves or the spinal cord. In adult mammals, neurons have a limited capacity to regenerate axons, leading to long-lasting or permanent issues with movement and sensation after nerve or spinal cord injuries.
The research indicates that active AHR signaling suppresses axon growth. When AHR is removed from neurons or its activity is blocked using drugs, damaged axonal fibers regenerate more successfully. In mouse models of peripheral nerve damage and spinal cord injury, suppressing AHR also resulted in better recovery of movement and sensation. The study further reveals that AHR supports a protective response in injured neurons, maintaining protein quality control (proteostasis) to help neurons withstand cellular stress, but this also limits the production of new proteins necessary for axon regeneration. Without active AHR, neurons prioritize the production of new proteins and activate biological pathways associated with growth and axon regeneration, a response that also involves another factor called HIF-1α. The discovery of AHR’s role in balancing neuronal survival and regeneration could have therapeutic implications, with existing AHR-inhibiting drugs undergoing clinical trials for other conditions potentially being investigated as treatments for neural injuries. However, the work is at an early stage, and further research is needed to assess the efficacy and safety of AHR-targeting strategies in patients. Source