Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal regeneration after spinal cord injury

Cell Death and Differentiation, 2014 · DOI: 10.1038/cdd.2014.14 · Published: February 21, 2014

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Following spinal cord injury (SCI), a protein called semaphorin 3A (Sema3A) stops axons from regenerating by attaching to a receptor complex. This study shows that galectin-1 (Gal-1), another protein, can also bind to this receptor complex in injured neurons. Gal-1's binding is dependent on sugar molecules (glycans). When Gal-1 binds, it blocks the Sema3A pathway, helping axons to regenerate and improving movement after SCI. The study suggests that using Gal-1 could be a potential treatment for SCI patients because it promotes the recovery of spinal lesions by blocking inhibitory signals.

Study Duration

7 days post SCI

Participants

Wild-type and galectin-1-deficient mice

Evidence Level

Level III, Animal study

Key Findings

1
Galectin-1 (Gal-1) promotes full locomotor functional recovery and that an early intervention with this lectin was sufﬁcient to prevent hindlimb loss of function after SCI.
2
Gal-1 induces microglia deactivation and prevents inflammation-induced neurodegeneration.
3
The neuroregenerative effects of Gal-1 are highly dependent on dimerization and cross-linking of cell surface glycans on NRP-1.

Research Summary

This study investigates the role of Galectin-1 (Gal-1) in promoting axonal regeneration and functional recovery after spinal cord injury (SCI). The results demonstrate that Gal-1 binds to the NRP-1/PlexinA4 receptor complex in injured neurons through a glycan-dependent mechanism, interfering with Sema3A signaling and promoting axonal regeneration. The study concludes that stable dimeric Gal-1 has therapeutic potential for treating SCI patients by blocking inhibitory signals and promoting restorative processes.

Practical Implications

Therapeutic Potential

Stable dimeric Gal-1 could be a potential agent for treating human SCI patients.

Early Intervention

Early intervention with Gal-1 can prevent hindlimb loss of function after SCI.

Microglia Deactivation

Gal-1's ability to deactivate microglia can contribute to neuroprotection and dampen pathogenic immune cells, leading to better restorative processes.

Study Limitations

1
The study was conducted on mice, and results may not directly translate to humans.
2
The coordinated locomotor behavior observed could be due to the arrangement of intraspinal neural circuits by the local axons regenerated most probably from interneurons, which make signal relay and synaptic connections with regenerated descending axonal tracts as previously described.
3
Future clinical studies should examine the relevance of endogenous Gal-1 in patients with neurological disorders.

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