Disinhibition of neurite growth to repair the injured adult CNS: Focusing on Nogo

Cellular and Molecular Life Sciences, 2008 · DOI: 10.1007/s00018-007-7170-3 · Published: November 3, 2007

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

After injuries to the adult brain or spinal cord, recovery of function is limited due to specific factors that inhibit neurite growth. Blocking these factors can lead to the growth of cultured neurons on inhibitory CNS tissue in vitro and regeneration of injured axons in vivo. The molecule Nogo-A and other glial-derived growth inhibitors restrict the regeneration and repair of disrupted neuronal circuits, thus limiting the functional recovery after CNS injuries. Nogo-A is found in the myelin sheaths of oligodendrocytes or are secreted into the extracellular matrix after injury, suppressing neurite growth in the adult CNS.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Neutralizing Nogo-A promotes axonal regeneration of various types of CNS neurons.
2
Damaged and spared fibres sprout above and below the SCI site after blocking Nogo-A function.
3
Blocking Nogo-A function improves the recovery of motor functions after SCI and stroke.

Research Summary

Investigations into mechanisms that restrict the recovery of functions after an injury to the brain or the spinal cord have led to the discovery of specific neurite growth inhibitory factors in the adult central nervous system (CNS) of mammals. Neutralizing Nogo-A either by applying function-blocking antibodies directed against the N-terminal region of Nogo-A or by interfering with Nogo-A receptors or signalling pathways boosts the regenerative response of injured adult CNS tracts, stimulates compensatory fibre growth and improves the recovery of lost functions Nogo-A antibody improves regeneration and locomotion of spinal cord-injured rats.

Practical Implications

Therapeutic Potential

Compounds that neutralize growth inhibitors or interfere with their downstream signalling are currently in clinical trials.

Clinical Translation Challenges

Translating experimental findings into clinical studies faces challenges such as the low incidence of SCI and the heterogeneity of spinal-cord-injured patients.

Future Treatment Regimes

Effective treatment may require a multidisciplinary approach combining reagents to overcome myelin inhibition, neurotrophic factors, and treatments to reduce the growth-suppressive properties of the glial scar, alongside intensive rehabilitative training.

Study Limitations

1
Different spinal levels and variable lesion anatomy imply that the population of spinal-cord-injured patients is very heterogeneous with respect to functional deficits and expected functional recovery.
2
If the onset of anti-Nogo-A antibody application after SCI is delayed for 1 or 2 weeks, the therapy is less effective in rats.
3
The lack of trophic support or the inhibitory glial scar, play additional important roles in preventing axons from regenerating successfully.

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