Mount Sinai researchers identify AHR protein as brake on nerve regeneration
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Researchers at the Icahn School of Medicine at Mount Sinai have identified the aryl hydrocarbon receptor (AHR) as a molecular brake that limits axon regrowth after nerve injury. Blocking AHR in mouse models of peripheral nerve and spinal cord damage improved recovery of movement and sensation. The findings, published in Nature, suggest a new therapeutic target for nerve repair.
Key Facts
- The study was published in the journal Nature.
- Blocking the aryl hydrocarbon receptor (AHR) promoted axon regeneration in mouse models of peripheral nerve and spinal cord injury.
- Suppressing AHR led to better recovery of movement and sensation in mice.
- AHR signaling shifts neurons toward stress management rather than rebuilding damaged connections, according to senior author Hongyan Zou.
- Without active AHR, neurons increase production of new proteins and activate growth pathways involving HIF-1α.
Molecular Brake Mechanism
The aryl hydrocarbon receptor (AHR) acts as a brake that shifts injured neurons toward managing stress rather than rebuilding damaged axons. Active AHR signaling suppresses axon growth, while removing AHR or blocking its activity with drugs allowed damaged axonal fibers to regenerate more successfully. In mouse models of peripheral nerve damage and spinal cord injury, suppressing AHR improved recovery of movement and sensation. Senior author Hongyan Zou, Professor of Neurosurgery and Neuroscience at the Icahn School of Medicine at Mount Sinai, described AHR as functioning like a brake.
Survival-Repair Tradeoff
Following injury, AHR supports a protective response that maintains protein quality control, known as proteostasis, helping neurons withstand cellular stress. This proteostasis response limits the production of new proteins required for rebuilding axons. Without active AHR, neurons increase production of new proteins and activate biological pathways associated with growth and axon regeneration. The regeneration response relies on another factor called HIF-1α, which helps control genes involved in metabolism and tissue repair. Dr. Zou explained that neurons use AHR to balance survival and regeneration, and releasing this brake pushes neurons into a state that favors repair.
Unexpected Toxin Sensor Role
AHR was first identified for its ability to detect environmental toxins and pollutants, termed xenobiotics. The new research reveals an unexpected role for AHR in regulating how neurons respond to injury. The findings suggest that blocking AHR could promote nerve regeneration and improve recovery after damage to peripheral nerves or the spinal cord.
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Mount Sinai researchers identify AHR protein as brake on nerve regeneration
