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  4. Co-targeting B-RAF and PTEN Enables Sensory Axons to Regenerate Across and Beyond the Spinal Cord Injury

Co-targeting B-RAF and PTEN Enables Sensory Axons to Regenerate Across and Beyond the Spinal Cord Injury

Frontiers in Molecular Neuroscience, 2022 · DOI: 10.3389/fnmol.2022.891463 · Published: April 26, 2022

Spinal Cord InjuryRegenerative MedicineNeurology

Simple Explanation

Adult mammals' primary sensory axons typically fail to regenerate after spinal cord injury (SCI) due to limited intrinsic growth potential. This study explores whether targeting B-RAF and PTEN can enhance axon regeneration. The researchers genetically targeted B-RAF and PTEN in DRG neurons of adult mice, observing that many dorsal column axons entered, crossed, and grew beyond the spinal cord lesion site. The study also found that post-injury targeting of B-RAF and PTEN enhances DC axon regeneration, suggesting a potential novel strategy for promoting long-distance regeneration of primary sensory axons.

Study Duration
3 weeks post-injury
Participants
Adult mice
Evidence Level
Not specified

Key Findings

  • 1
    Genetically targeting B-RAF and PTEN in DRG neurons of adult mice enables many DC axons to enter, cross, and grow beyond the lesion site after SCI, with some axons reaching approximately 2 mm rostral to the lesion by 3 weeks post-injury.
  • 2
    Co-targeting B-RAF and PTEN promotes more robust DC regeneration than a pre-conditioning lesion, which additively enhances the regeneration triggered by B-RAF/PTEN.
  • 3
    Post-injury targeting of B-RAF and PTEN enhances DC axon regeneration, demonstrating that this co-targeting effectively enhances the intrinsic growth potential of DC axons after SCI.

Research Summary

This study investigates whether concurrent B-RAF activation and PTEN deletion promotes dorsal column axon regeneration after SCI. The results demonstrate that co-targeting B-RAF and PTEN effectively enhances the intrinsic growth potential of DC axons after SCI. The study found that genetically targeting B-RAF and PTEN selectively in DRG neurons of adult mice enables many DC axons to enter, cross, and grow beyond the lesion site after SCI. It was also found that post-injury targeting of B-RAF and PTEN enhances DC axon regeneration, suggesting that this may help to develop a novel strategy to promote robust long-distance regeneration of primary sensory axons.

Practical Implications

Therapeutic Potential for SCI

The findings suggest that co-targeting B-RAF and PTEN could be a potential therapeutic strategy for promoting axon regeneration after spinal cord injury.

Enhancing Intrinsic Growth Potential

The study highlights the importance of enhancing the intrinsic growth potential of neurons for successful axon regeneration in the CNS.

Combination Therapies

The additive effect of B-RAF/PTEN co-targeting with pre-conditioning lesion suggests that combination therapies targeting multiple pathways may be more effective for promoting axon regeneration.

Study Limitations

  • 1
    The mechanisms by which B-RAF activation with PTEN deletion powerfully and synergistically promotes DC axon regeneration remain unclear.
  • 2
    The extent of DC regeneration elicited by individually activating B-RAF or deleting PTEN was not examined in the SCI context.
  • 3
    Differences in injury models may contribute to the differences observed when compared to other studies.

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