Plexina2 and CRMP2 Signaling Complex Is Activated by Nogo-A-Liganded Ngr1 to Restrict Corticospinal Axon Sprouting after Trauma

The Journal of Neuroscience, 2019 · DOI: https://doi.org/10.1523/JNEUROSCI.2996-18.2019 · Published: April 24, 2019

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

After brain or spinal cord trauma, the interaction of Nogo-A with neuronal NgR1 limits regenerative axonal sprouting and functional recovery. The Nogo-A-induced association of NgR1 with CRMP2 requires PlexinA2 as a coreceptor. Thus, a NgR1/PlexinA2/CRMP2 ternary complex limits neural repair after adult mammalian CNS trauma.

Study Duration

Not specified

Participants

Mixed female and male double-heterozygous cohort of mice

Evidence Level

Not specified

Key Findings

1
Nogo-A induces the association of NgR1 with CRMP2, and this requires PlexinA2 as a coreceptor.
2
Inhibition of cortical axon regeneration by Nogo-A depends on a NgR1/PlexinA2 genetic interaction.
3
NgR1 and PlexinA2 interact genetically in vivo to restrict corticospinal sprouting in mouse cervical spinal cord after unilateral pyramidotomy.

Research Summary

After brain or spinal cord trauma, interaction of Nogo-A with neuronal NgR1 limits regenerative axonal sprouting and functional recovery. The Nogo-A-induced association of NgR1 with CRMP2 requires PlexinA2 as a coreceptor. Thus, a NgR1/PlexinA2/CRMP2 ternary complex limits neural repair after adult mammalian CNS trauma.

Practical Implications

Targeted Therapies

Development of targeted therapies to disrupt the NgR1/PlexinA2/CRMP2 complex could promote axonal regeneration and functional recovery after CNS trauma.

Understanding CNS Repair

The study enhances our understanding of the molecular mechanisms underlying neural repair after CNS trauma and links them to developmental processes.

Drug Development

These data may help drug development by suggesting that combinatorial therapies targeting both NgR1 and PlexinA2 pathways may have synergistic effects on promoting neural repair.

Study Limitations

1
The study primarily focuses on corticospinal neurons; the findings may not be generalizable to other neuronal types or CNS regions.
2
The genetic interaction between NgR1 and PlexinA2 was assessed using heterozygous mice; the effects of homozygous deletion of both genes were not investigated.
3
The study identifies a specific signaling complex involved in Nogo-A-mediated growth inhibition, but does not fully elucidate the downstream signaling events or potential therapeutic targets.

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