Complement Protein C3 Suppresses Axon Growth and Promotes Neuron Loss

Scientific Reports, 2017 · DOI: 10.1038/s41598-017-11410-x · Published: September 29, 2017

Simple Explanation

This study investigates the role of complement C3, an inflammatory protein, in nerve regeneration and neuron survival after spinal cord injury (SCI). The researchers found that mice lacking C3 showed better nerve regeneration compared to normal mice. In lab experiments, adding C3 worsened the nerve growth inhibition caused by myelin, a substance that can hinder nerve repair. Further experiments suggest that a fragment of C3, called C3b, is responsible for these negative effects. These findings suggest that C3 plays a role in limiting nerve regeneration and harming neurons after spinal cord injury, highlighting a previously unknown function of this inflammatory protein in the central nervous system.

Study Duration

6 weeks

Participants

Mice (C3+/+ and C3−/−), rat cortical cells, adult mouse DRG cells

Evidence Level

Not specified

Key Findings

1
C3−/− mice demonstrated a 2-fold increase in sensory axon regeneration in the spinal cord compared to wildtype C3+/+ mice 6 weeks after dorsal hemisection with peripheral conditioning lesion.
2
In vitro, addition of C3 tripled both myelin-mediated neurite outgrowth inhibition and neuron loss versus myelin alone.
3
Purified C3b is responsible for the growth inhibitory and neurotoxic or anti-adhesion activities of C3.

Research Summary

The study investigates the role of complement protein C3 in axon regeneration and neuronal survival following spinal cord injury (SCI). The findings demonstrate that C3 deficiency enhances sensory fiber regrowth and potentially offers neuroprotection after SCI. In vitro experiments reveal that C3 exacerbates myelin-mediated neurite outgrowth inhibition and neuron loss, with C3b identified as a key mediator of these effects.

Practical Implications

Therapeutic Target

Inhibition of C3, particularly C3b, could be a potential therapeutic strategy to promote axon regeneration and improve outcomes after spinal cord injury.

Novel Mechanism

The discovery that myelin-associated serine proteases can cleave C3 provides a new understanding of how complement activation is initiated in the CNS.

Non-Traditional Role

This study highlights the non-immune functions of complement proteins in the CNS, specifically their role in regulating axon growth and neuronal survival.

Study Limitations

1
The study primarily focuses on sensory axon regeneration, and further research is needed to investigate the effects on motor tract axon regeneration.
2
The in vitro experiments used primary neuronal cultures, which may not fully replicate the complex in vivo microenvironment of the injured spinal cord.
3
The precise mechanisms by which C3/C3b induce neuronal cell death or inhibit cell adhesion require further investigation.

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