Leukocyte Common Antigen-Related Phosphatase Is a Functional Receptor for Chondroitin Sulfate Proteoglycan Axon Growth Inhibitors

The Journal of Neuroscience, 2011 · DOI: 10.1523/JNEUROSCI.1737-11.2011 · Published: October 5, 2011

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Chondroitin sulfate proteoglycans (CSPGs) are molecules that can prevent axons from regrowing after an injury to the central nervous system. This study identifies a receptor, LAR, on nerve cells that binds CSPGs. When CSPGs bind to LAR, it inhibits the growth of axons. Blocking LAR can overcome this inhibition and promote axon growth, suggesting a potential therapeutic target for CNS injuries. The scientists found that by blocking the LAR receptor, they could stimulate axon growth in mice with spinal cord injuries, leading to improved functional recovery.

Study Duration

5 Weeks

Participants

Adult female C57BL/6 mice (8–10 weeks of age)

Evidence Level

Level II: Experimental study

Key Findings

1
CSPGs bind to the LAR phosphatase with high affinity in COS-7 cells, indicating a direct interaction between these molecules.
2
Deleting or blocking LAR function overcomes the growth-inhibitory effects of CSPGs on neurite outgrowth in neuronal cultures, suggesting that LAR mediates CSPG's inhibitory effects.
3
Systemic treatment with LAR-targeting peptides promotes axonal growth of descending serotonergic fibers and locomotor functional recovery in mice with spinal cord injuries.

Research Summary

This study identifies leukocyte common antigen-related phosphatase (LAR) as a functional receptor for chondroitin sulfate proteoglycans (CSPGs), which are known axon growth inhibitors. The researchers found that CSPGs bind to LAR with high affinity, enhancing LAR phosphatase activity, and that blocking LAR overcomes CSPG-mediated growth inhibition. In vivo experiments demonstrated that LAR-targeting peptides promote axonal regeneration and functional recovery in mice with spinal cord injuries, suggesting LAR as a therapeutic target.

Practical Implications

Therapeutic Target

LAR phosphatase represents a novel therapeutic target for promoting axonal regeneration and functional recovery after CNS injuries.

Drug Development

Development of LAR-targeting drugs may offer a more effective strategy for overcoming CSPG-mediated growth inhibition compared to existing methods like ChABC.

Clinical Applications

The findings have potential clinical applications for treating neurological disorders involving axonal outgrowth inhibition, such as spinal cord injury, brain trauma, and white matter stroke.

Study Limitations

1
The study primarily focuses on the role of LAR in CSPG-mediated inhibition, while other receptors and mechanisms may also contribute.
2
The in vivo experiments were conducted using a specific spinal cord injury model, and the results may not be generalizable to all types of CNS injuries.
3
The long-term effects and potential side effects of LAR-targeting peptides were not fully investigated in this study.

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