Aptamer Antagonists of Myelin-Derived Inhibitors Promote Axon Growth

PLoS ONE, 2010 · DOI: 10.1371/journal.pone.0009726 · Published: March 16, 2010

Simple Explanation

The myelin surrounding nerve fibers in the adult central nervous system inhibits axon regeneration after injury. Three major myelin-derived inhibitors (Nogo, MAG, and OMgp) bind to the Nogo-66 receptor (NgR) on axons, limiting neurite outgrowth. This study demonstrates that RNA aptamers can bind to NgR, compete with these inhibitors, and promote axon elongation in vitro, suggesting their potential as neuromodulators and for treating neuronal damage.

Study Duration

Not specified

Participants

Not specified

Evidence Level

In vitro study

Key Findings

1
RNA aptamers can be generated that bind with high affinity to NgR.
2
These aptamers compete with myelin-derived inhibitors (Nogo, MAG, and OMgp) for binding to NgR.
3
The aptamers promote axon elongation of neurons in vitro, even in the presence of myelin-derived inhibitors.

Research Summary

This study demonstrates that RNA aptamers can be selected to bind the Nogo-66 receptor (NgR) and compete with myelin-derived inhibitors of axon regeneration for binding to the receptor. Neurite outgrowth assays confirmed that these aptamers can reverse the inhibitory effects of myelin-derived inhibitors in vitro. The unexpected finding of NgR expression on Schwann cells suggests a potential role for these cells in modulating the inhibitory environment in the nervous system.

Practical Implications

Therapeutic Potential for CNS Injuries

Aptamers may offer a novel therapeutic approach to overcome myelin-associated inhibition of axon regeneration following CNS injuries, such as spinal cord injury.

Neuromodulation

Aptamers can be valuable tools in modulating and redefining normal neuronal architectures.

Understanding NgR Function

The discovery of NgR expression on Schwann cells opens new avenues for understanding the role of NgR in nerve regeneration and repair in the PNS.

Study Limitations

1
The aptamers did not compete with peptides as well as their affinity constants might have indicated.
2
The study was performed in vitro, and further studies are needed to evaluate the aptamers' efficacy in vivo and in serum.
3
The age-dependent expression of NgR in Schwann cells suggests that results may vary based on age.

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