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ErbB1 epidermal growth factor receptor is a valid target for reducing the effects of multiple inhibitors of axonal

Veronica H L Leinster1, Mary T Joy, Raisa E Vuononvirta

  • 1Research Department of Cell and Developmental Biology, UK.

Experimental Neurology
|October 2, 2012
PubMed

Insights

Epidermal growth factor receptor (ErbB1) inhibitors promote axonal regeneration by targeting CNS myelin and other inhibitory molecules. This study confirms ErbB1

Area of Science:

  • Neuroscience
  • Cell Biology
  • Regenerative Medicine

Background:

  • Central nervous system (CNS) myelin inhibits axonal regeneration after injury.
  • Epidermal growth factor receptor (ErbB1) signaling has been implicated in this inhibition.
  • Concerns exist regarding off-target effects of ErbB1 inhibitors.

Purpose of the Study:

  • To investigate the specific role of ErbB1 in inhibiting axonal regeneration.
  • To validate ErbB1 kinase activity as a therapeutic target for promoting CNS repair.

Main Methods:

  • Culturing neurons from ErbB1 knockout (ErbB1-/-) mice.
  • Exposing neurons to CNS myelin, chondroitin sulfate proteoglycans (CSPG), fibrinogen, and polyinosinic:polycytidylic acid (poly I:C).
  • Assessing neurite outgrowth and ErbB1 activation.

Main Results:

  • ErbB1 activation was confirmed in neurons exposed to axonal regeneration inhibitors.
  • ErbB1-/- neurons exhibited enhanced neurite outgrowth compared to wild-type neurons.
  • ErbB1 kinase inhibitors did not further improve outgrowth in ErbB1-/- neurons, excluding off-target effects.

Conclusions:

  • ErbB1 kinase activity is a valid target for promoting axonal regeneration.
  • Inhibiting ErbB1 can overcome the regenerative blockade imposed by CNS myelin and other inhibitory molecules.
  • This finding supports therapeutic strategies for CNS injury recovery.

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