Axonal Regeneration: Underlying Molecular Mechanisms and Potential Therapeutic Targets

Biomedicines, 2022 · DOI: https://doi.org/10.3390/biomedicines10123186 · Published: December 8, 2022

Regenerative Medicine Neurology Genetics

Simple Explanation

Axons in the peripheral nervous system can repair themselves after damage, unlike those in the central nervous system. This difference is crucial in spinal cord, brain, and peripheral nerve injuries, where axonal regrowth is often disrupted. Intrinsic growth factors significantly aid axonal regeneration in injured nerves. Factors like protein profiles, microtubule stability, and signaling pathways distinguish the self-renewal capacity of central versus peripheral axons. However, glial scar development, myelin-associated inhibitors, insufficient neurotrophic factors, and inflammatory reactions hinder axonal regeneration. This review explores these mechanisms and potential therapeutic targets to promote quicker axonal healing.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
The review identifies various molecular pathways activated after nerve injury, such as cAMP, MAPK, and RhoA/ROCK/LIMK, as significant in axonal regeneration.
2
Growth factors, microRNAs, and astrocytes also play commendable roles in axonal regeneration, highlighting their potential as therapeutic targets.
3
Prospective targets are identified to bridge knowledge gaps in the molecular pathways underlying regeneration, aiming to create more powerful strategies for encouraging axonal regeneration after nervous system injury.

Research Summary

This review discusses the detailed mechanisms of various molecular pathways involved in axonal regeneration, emphasizing key players that could be valuable therapeutic targets for quick axonal healing. The study identifies potential targets to address knowledge gaps in molecular pathways of regeneration, aiming to develop more effective strategies to promote axonal regeneration post-nervous system injury. Peripheral nerves can regenerate with the support of Schwann cells and rapid debris clearance by macrophages, while central nerves, lacking intrinsic growth factors and facing inhibitory molecules from oligodendrocytes, cannot regenerate.

Practical Implications

Therapeutic Targets

Identified signalling molecules like cAMP, STAT3, AKT, and BDNF can serve as therapeutic targets to restore function in injured axons.

Downregulation Strategies

Downregulating GSK-3β, PTEN, and SOCS3 and myelin-associated inhibitors can modify the fate of regenerating axons.

Clinical Approaches

Developing valid and affordable clinical approaches is crucial for functional axon recovery.

Study Limitations

1
A valid and affordable clinical approach for functional axon recovery is still nonexistent.
2
Excessive stress on peripheral nerves may irreversibly damage axons and inhibit regrowth.
3
Central nerves cannot regenerate since they do not have enough intrinsic growth factors.

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