Neuronal intrinsic barriers for axon regeneration in the adult CNS

Curr Opin Neurobiol, 2010 · DOI: 10.1016/j.conb.2010.03.013 · Published: August 1, 2010

Simple Explanation

A significant obstacle to recovery after spinal cord injury is the failure of damaged nerve fibers (axons) to regrow and re-establish connections. Overcoming this has been a major research focus. Research suggests that simply blocking external inhibitors of axon growth isn't enough. The diminished capacity of mature nerve cells to regenerate themselves is a key factor in this failure. This review explores the molecular mechanisms that regulate the inherent ability of adult central nervous system (CNS) axons to grow, and how this knowledge could inform new therapeutic approaches.

Study Duration

Not specified

Participants

Different species and different models

Evidence Level

Review

Key Findings

1
Removing extracellular inhibitory activities is insufficient for successful axon regeneration in the adult CNS.
2
Diminished intrinsic regenerative ability of mature neurons is a major contributor to regeneration failure.
3
SOCS3 deletion promotes optic nerve regeneration in vivo.

Research Summary

The review addresses the challenge of why injured axons in the adult mammalian CNS fail to regenerate after injury. It discusses the limitations of solely targeting extracellular inhibitory molecules and highlights the importance of the intrinsic regenerative ability of mature neurons. The authors summarize molecular mechanisms regulating intrinsic axon growth capacity and their therapeutic implications.

Practical Implications

Therapeutic Strategies

Understanding intrinsic barriers can lead to novel therapeutic targets.

Combinatorial Approaches

Combining strategies addressing both extrinsic and intrinsic factors may be more effective.

Targeting Negative Regulators

Identifying and modulating negative regulators of axon regeneration pathways may enhance regeneration.

Study Limitations

1
The exact mechanisms mediating changes in mTOR activity during development and after injury are largely unknown.
2
It remains to be determined whether local protein synthesis in axons or translation in the soma is crucial for axon regeneration.
3
The roles of microRNA in axon growth and regeneration await to be explored.

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