The Calcium Channel Subunit Alpha2delta2 Suppresses Axon Regeneration in the Adult CNS

Neuron. 2016 Oct 19;92(2):419-434. doi: 10.1016/j.neuron.2016.09.026. Epub 2016 Oct 6.


Injuries to the adult CNS often result in permanent disabilities because neurons lose the ability to regenerate their axon during development. Here, whole transcriptome sequencing and bioinformatics analysis followed by gain- and loss-of-function experiments identified Cacna2d2, the gene encoding the Alpha2delta2 subunit of voltage-gated calcium channels (VGCCs), as a developmental switch that limits axon growth and regeneration. Cacna2d2 gene deletion or silencing promoted axon growth in vitro. In vivo, Alpha2delta2 pharmacological blockade through Pregabalin (PGB) administration enhanced axon regeneration in adult mice after spinal cord injury (SCI). As PGB is already an established treatment for a wide range of neurological disorders, our findings suggest that targeting Alpha2delta2 may be a novel treatment strategy to promote structural plasticity and regeneration following CNS trauma.

MeSH terms

  • Animals
  • Axons / drug effects
  • Axons / physiology*
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / genetics*
  • Calcium Channels / metabolism
  • Central Nervous System
  • Female
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / metabolism
  • Gene Expression Profiling
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neuronal Outgrowth / drug effects
  • Neuronal Outgrowth / genetics*
  • Neurons / metabolism*
  • Pregabalin / pharmacology
  • RNA, Messenger / metabolism
  • Regeneration / drug effects
  • Regeneration / genetics*
  • Sequence Analysis, RNA
  • Spinal Cord Injuries / metabolism*


  • Cacna2d2 protein, mouse
  • Calcium Channel Blockers
  • Calcium Channels
  • RNA, Messenger
  • Pregabalin