Research ArticleNeuroscience

The nociceptin receptor inhibits axonal regeneration and recovery from spinal cord injury

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Science Signaling  03 Apr 2018:
Vol. 11, Issue 524, eaao4180
DOI: 10.1126/scisignal.aao4180

Releasing the brakes on axonal regeneration

Recovery of motor function after an injury that severs spinal cord tracts is limited by multiple inhibitors of axonal regeneration, such as the myelin-associated protein Nogo. Sekine et al. identified ORL1, a receptor for the opioid peptide nociceptin, as another inhibitor of axonal regeneration. ORL1 suppressed axonal regeneration by increasing the cell surface abundance of the Nogo receptor NgR1 and through NgR1-independent mechanisms. Recovery of locomotor function and axonal regeneration were improved in mice treated with an ORL1 antagonist after spinal cord injury, and these effects were accentuated in NgR1-deficient mice. Thus, combining ORL1 and NgR1 antagonists may yield greater improvements in locomotor function after spinal cord injury than has been possible with NgR1 antagonists alone.