Inhibition and enhancement of neural regeneration by chondroitin sulfate proteoglycans

Neural Regeneration Research, 2017 · DOI: 10.4103/1673-5374.206630 · Published: May 1, 2017

Regenerative Medicine Physiology Neurology

Simple Explanation

Chondroitin sulfate proteoglycans (CSPGs) are generally thought to inhibit regeneration in the adult central nervous system. However, this study suggests that CSPGs can promote regeneration when certain factors are present. HB-GAM (Heparin-binding growth-associated molecule) is identified as a molecule that can change the role of CSPGs from inhibitory to active in regeneration. HB-GAM appears to reverse the inhibitory effects of CSPGs by binding to them and then interacting with neuron surface receptors, ultimately promoting neurite outgrowth and regeneration.

Study Duration

Not specified

Participants

Transgenic mice with fluorescent axons/dendrites

Evidence Level

In vitro and in vivo studies

Key Findings

1
HB-GAM can reverse the inhibitory effect of CSPGs on neurite outgrowth in vitro, promoting growth instead.
2
In vivo, HB-GAM injection leads to dendrite regeneration in the cerebral cortex after prick-injury, a phenomenon not previously demonstrated in mammalian nervous system injuries.
3
HB-GAM induces axonal regeneration in the spinal cord, increasing the number and growth rate of axons traversing injury sites.

Research Summary

This study explores the dual role of chondroitin sulfate proteoglycans (CSPGs) in neural regeneration, highlighting their potential to switch from inhibitors to promoters of regeneration under specific conditions. Heparin-binding growth-associated molecule (HB-GAM) is presented as a key factor in modulating CSPG activity, facilitating neurite outgrowth and regeneration both in vitro and in vivo. The research demonstrates that HB-GAM promotes dendrite and axon regeneration in the cerebral cortex and spinal cord, respectively, suggesting new avenues for drug development for CNS injuries.

Practical Implications

Therapeutic Potential

HB-GAM could be a therapeutic target for promoting neural regeneration after CNS injuries.

Understanding CSPG Roles

A deeper understanding of CSPG interactions can lead to better strategies for manipulating the ECM to facilitate repair.

Dendrite Regeneration

The finding that dendrites can regenerate opens new possibilities for treating conditions like traumatic brain injury and stroke.

Study Limitations

1
The precise mechanism by which glypican-2 ligation leads to enhanced neurite regrowth requires further investigation.
2
The extent to which injected HB-GAM enhances functional recovery in different injury models still needs further investigation.
3
Formal safety studies on using HB-GAM as a therapeutic strategy are still lacking.

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