Targeting chondroitinase ABC to axons enhances the ability of chondroitinase to promote neurite outgrowth and sprouting

PLOS ONE, 2020 · DOI: https://doi.org/10.1371/journal.pone.0221851 · Published: January 21, 2020

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This research investigates a potential treatment for spinal cord injuries by promoting nerve regeneration. The approach involves using an enzyme called chondroitinase ABC (ChABC) to break down molecules that inhibit nerve growth. The study explores whether directing ChABC specifically to the axon, the long, slender projection of a nerve cell, can enhance its ability to promote nerve outgrowth and sprouting. The findings suggest that targeting ChABC to the axon significantly boosts its effectiveness in stimulating neurite extension, indicating a promising strategy for promoting long-distance axon regeneration following spinal cord injury.

Study Duration

Not specified

Participants

SH-SY5Y cells, Dorsal Root Ganglion neurons (DRGs) from adult Sprague-Dawley rats

Evidence Level

In vitro study

Key Findings

1
Targeting ChABC to the axon significantly enhances its ability to promote neurite outgrowth compared to non-targeted ChABC.
2
ChABC expression in neurons up-regulates cell surface expression of β-integrin, a cell adhesion molecule, particularly in the axonal compartment when ChABC is targeted.
3
ChABC expression reduces intracellular levels of RhoA and PTEN, molecules known to inhibit axon regeneration.

Research Summary

This study demonstrates that targeting chondroitinase ABC (ChABC) to the axon markedly enhances its ability to promote neurite extension and sprouting in neuronal cultures. The enhanced neurite outgrowth is associated with increased expression of β1-integrin at the axonal cell surface and activation of focal adhesion kinase, indicating enhanced cell adhesion. Furthermore, ChABC expression leads to a decrease in RhoA and PTEN levels, identifying two key pathways through which ChABC promotes neurite outgrowth.

Practical Implications

Enhanced Spinal Cord Injury Treatment

Targeting ChABC to the axon may be a more effective strategy for promoting long-distance axon regeneration following spinal cord injury.

Broader Therapeutic Applications

This approach could potentially improve the efficacy of ChABC in treating other conditions, such as myocardial infarction, stroke, and Parkinson’s disease, where it has shown promise.

Combination Therapies

The findings support the inclusion of ChABC as a key component in combination therapies for spinal cord injury, particularly when combined with PTEN knockdown strategies.

Study Limitations

1
The study primarily uses an in vitro model, which may not fully replicate the complex environment of the injured spinal cord in vivo.
2
Transfection efficiencies in some experiments were relatively low, which could affect the magnitude of the observed effects.
3
The study focused on specific cell lines (SH-SY5Y) and DRGs, and further research is needed to confirm these findings in other neuronal types and in vivo models.

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