Inhibition of Gamma-Secretase Promotes Axon Regeneration After a Complete Spinal Cord Injury

Front. Cell Dev. Biol., 2020 · DOI: 10.3389/fcell.2020.00173 · Published: March 20, 2020

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates how to promote axon regeneration after spinal cord injury using sea lampreys as a model. Researchers found that inhibiting gamma-secretase, a protein involved in the Notch signaling pathway, enhances axon regeneration in lampreys after complete spinal cord injury. The findings suggest that gamma-secretase could be a potential target for promoting axon regeneration after nervous system injuries.

Study Duration

11 weeks

Participants

149 larval sea lampreys

Evidence Level

Not specified

Key Findings

1
Gamma-secretase inhibition reduces HESB expression in the brainstem of spinal cord injured lampreys.
2
Inhibition of gamma-secretase significantly promotes axon regeneration of individually identifiable descending neurons after complete spinal cord injury.
3
Gamma-secretase inhibition increases the number of regenerated axons in the spinal cord following complete SCI.

Research Summary

The study investigates the effects of inhibiting gamma-secretase on axon regeneration after spinal cord injury in lampreys. RNA-Seq analysis revealed downregulation of a HES transcription factor (HESB) and enrichment of the Notch signaling pathway after GABA and baclofen treatments. Pharmacological inhibition of gamma-secretase promoted axon regeneration and reduced HESB expression in the brainstem of spinal cord injured animals.

Practical Implications

Therapeutic Target

Gamma-secretase could be a novel therapeutic target to promote axon regeneration after nervous system injuries, including spinal cord injury.

Drug Development

Development of specific gamma-secretase inhibitors could be explored for potential use in treating spinal cord injuries.

Further Research

Further studies should evaluate the effects of gamma-secretase inhibition in preclinical mammalian models of spinal cord injury.

Study Limitations

1
The study was conducted on lampreys, and results may not directly translate to mammals.
2
The study used a pharmacological inhibitor of gamma-secretase, which may have off-target effects.
3
The study did not investigate the long-term functional outcomes of enhanced axon regeneration.

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