Low-density Lipoprotein Receptor-related Protein 1 (LRP1)-dependent Cell Signaling Promotes Axonal Regeneration

JOURNAL OF BIOLOGICAL CHEMISTRY, 2013 · DOI: 10.1074/jbc.M113.478552 · Published: September 13, 2013

Simple Explanation

This study investigates the role of LRP1, a receptor involved in cell signaling, in promoting axonal regeneration after spinal cord injury. The researchers found that activating LRP1 with specific molecules enhances the growth of nerve fibers in the central nervous system. These findings suggest that LRP1 could be a potential therapeutic target for treating neurological disorders by promoting nerve regeneration.

Study Duration

4 weeks

Participants

Adult female Fisher 344 rats weighing 150–200 g

Evidence Level

Not specified

Key Findings

1
LRP1 activation promotes neurite outgrowth from adult DRG sensory neurons under both permissive and non-permissive conditions.
2
LRP1 ligands elicit TrkC signaling in DRG neurons by transactivation of the LRP1 receptor.
3
Intrathecal infusions of RBD (an LRP1 ligand) promote axonal sprouting and regeneration after spinal cord injury.

Research Summary

This study identifies a novel mechanism for promoting axonal sprouting and regeneration in the CNS in vivo: the targeting of LRP1 receptors. Agonists of this LDL gene family receptor result in activation of canonical Trk signaling in a SFK-dependent manner, resulting in ERK and Akt activation. Intrathecal infusions of LRP1 agonists result in significant increases in axonal sprouting and regeneration after spinal cord injury.

Practical Implications

Therapeutic Target for CNS Injury

Targeting LRP1 receptors could offer a novel therapeutic approach for promoting axonal regeneration after CNS injuries, such as spinal cord injury.

Understanding Neurotrophin Signaling

The finding that LRP1 agonists can stimulate neurotrophin receptors (Trk receptors) provides new insights into how to modulate neurotrophin signaling for therapeutic benefit.

Drug Development

Development of small molecules or bioactive peptides that selectively bind and activate LRP1-dependent cell signaling could lead to more effective treatments for nervous system injury and degeneration.

Study Limitations

1
Functional outcomes were not studied due to the location of the spinal cord transection.
2
The study focused on a specific population of DRG neurons (TrkC-expressing) and may not be generalizable to all neuronal populations.
3
The potential for non-targeted sprouting induced by LRP1 agonists to worsen functional outcomes needs to be addressed.

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