The effect of systemic PTEN antagonist peptides on axon growth and functional recovery after spinal cord injury

Biomaterials, 2014 · DOI: 10.1016/j.biomaterials.2014.02.037 · Published: May 1, 2014

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study explores a new way to promote nerve fiber regrowth after spinal cord injury using PTEN antagonist peptides (PAPs). These peptides are designed to block the activity of PTEN, a protein that inhibits nerve fiber growth. The research found that administering PAPs after spinal cord injury in mice led to increased growth of nerve fibers in the spinal cord. Specifically, the growth of descending serotonergic fibers and sprouting of corticospinal fibers were observed. Importantly, the PAP treatment also enhanced the recovery of locomotor function in the injured mice, suggesting that this approach could be a potential therapeutic strategy for CNS injuries.

Study Duration

5 weeks

Participants

Adult female C57BL/6 mice (9–10 weeks old)

Evidence Level

Not specified

Key Findings

1
Systemic administration of PTEN antagonist peptides (PAPs) stimulated the growth of descending serotonergic fibers in the caudal spinal cord of adult mice after dorsal over-hemisection injury.
2
PAPs induced significant sprouting of corticospinal fibers in the rostral spinal cord and limited growth of corticospinal axons in the caudal spinal cord.
3
PAP treatment enhanced the recovery of locomotor function in adult rodents with spinal cord injury.

Research Summary

The study identifies PTEN antagonist peptides (PAPs) that selectively block PTEN, a negative regulator of axon growth, by targeting its critical functional domains. Systemic administration of PAPs after spinal cord injury in mice stimulated growth of descending serotonergic fibers, induced sprouting of corticospinal fibers, and enhanced recovery of locomotor function. The findings suggest that systemically deliverable PAPs may offer therapeutic advantages for promoting axon growth and functional recovery after CNS axonal injuries.

Practical Implications

Therapeutic Potential

Systemically deliverable PAPs might have therapeutic advantages over more invasive therapies and facilitate development of a successful therapy for CNS axonal injuries.

Drug Development

This study may facilitate development of effective therapeutic agents for CNS injuries using small peptides to block PTEN selectively.

Combination Therapies

Peptides can be combined with other effective strategies, such as small peptides to block scar-mediated suppression, to target multiple mechanisms for neuronal growth failure.

Study Limitations

1
The study employed a partial injury model, making it difficult to differentiate between regeneration of severed axons and sprouting of spared axons.
2
The study initiated PAP treatments 2 days after axon lesion, whereas earlier intervention might yield better results.
3
The long-term safety of PTEN inhibition with PAP treatment needs further assessment, given PTEN's role in various cellular functions.

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