Traffic lights for axon growth: proteoglycans and their neuronal receptors

Neural Regeneration Research, 2014 · DOI: 10.4103/1673-5374.128236 · Published: February 1, 2014

Regenerative Medicine Physiology Neurology

Simple Explanation

Axon growth is a crucial part of nervous system development and its ability to recover after injury. Like traffic signals, certain molecules either encourage or discourage axon growth. Chondroitin sulfate proteoglycans (CSPGs) and heparan sulfate proteoglycans (HSPGs) act like these signals, often causing axons to either stop or grow, respectively. Recent discoveries have identified LAR and NgR family molecules as receptors for CSPGs and HSPGs, providing tools to study axon growth and potential therapeutic targets for regeneration.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
CSPGs and HSPGs have opposite effects on axonal behavior, with CSPGs often acting as repulsive guidance molecules and HSPGs as attractive signals.
2
The LAR family RPTPs, including PTPsigma, PTPdelta, and LAR, serve as neuronal receptors for both CSPGs and HSPGs, mediating intracellular signaling and influencing neurite extension.
3
NgR1 and NgR3 are also functional receptors of CSPGs, sharing a molecular platform with myelin-associated inhibitors (MAIs) and serving as a signal converging point for axon growth inhibitors.

Research Summary

Axon growth is crucial for nervous system development and post-injury recovery. CSPGs and HSPGs, acting like traffic signals, respectively inhibit and promote axon growth. The identification of LAR and NgR family molecules as receptors for CSPGs and HSPGs offers molecular tools for studying axon growth regulation and potential therapeutic targets for promoting regeneration. Functional redundancy among CSPG receptors suggests that a combinational targeting strategy interfering with multiple receptors may be necessary to promote post-injury axon regeneration.

Practical Implications

Therapeutic Target Identification

Proteoglycan receptors are potential therapeutic targets for promoting post-injury axon regeneration.

Combinatorial Treatment Strategies

A combinational targeting strategy that simultaneously interferes with multiple CSPG receptors may be necessary to achieve an optimal result in promoting post-injury axon regeneration.

Spinal Cord Injury Treatment

An optimal treatment regime should take into account both the axons and cell bodies of the injured neurons so as to maximize the opportunity for functional recovery.

Study Limitations

1
The precise mechanisms underlying bimodal signaling of HSPGs and CSPGs through the same neuronal receptor (PTPsigma) are not fully understood.
2
The biological relevance of HS-Ngr1 interaction has not been characterized, leaving an interesting topic for future studies.
3
It is not clear what results in the discrepancy between the in vitro and in vivo effects of LAR deficiency.

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