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Integrin activation promotes axon growth on inhibitory chondroitin sulfate proteoglycans by enhancing integrin

Chin Lik Tan1, Jessica C F Kwok, Rickie Patani

  • 1Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0PY, United Kingdom.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|April 29, 2011
PubMed

Insights

Chondroitin sulfate proteoglycans (CSPGs) inhibit axon regeneration by inactivating integrins. Activating integrins can overcome this inhibition, promoting axon growth after CNS injury.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Regenerative Medicine

Background:

  • Chondroitin sulfate proteoglycans (CSPGs) increase after central nervous system (CNS) lesions.
  • CSPGs inhibit axon regeneration, hindering recovery from neurological damage.

Purpose of the Study:

  • To investigate if CSPGs inhibit axon regeneration by inactivating integrin receptors.
  • To determine if forcing integrin activation can overcome CSPG-mediated inhibition.

Main Methods:

  • Cultured rat sensory neurons and human embryonic stem cell-derived motoneurons were used.
  • Integrin signaling pathways, including phosphorylated FAK (pFAK) and pSrc, were analyzed.
  • The effects of CSPGs (aggrecan) and integrin activators (manganese, TS2/16 antibody) on axon growth were assessed.

Main Results:

  • Aggrecan inhibited laminin-mediated axon growth by impairing integrin signaling, reducing pFAK and pSrc levels.
  • Forcing integrin activation with manganese or TS2/16 reversed aggrecan's inhibitory effects.
  • Integrin activation enhanced axon growth in both sensory neurons and motoneurons.
  • Nogo-A inhibition was also reversed by integrin activation.

Conclusions:

  • CSPGs inhibit axon regeneration by inactivating integrins.
  • Integrin activation is a promising strategy to promote axon regeneration after CNS injury.

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