The Calcium Channel Subunit Alpha2delta2 Suppresses Axon Regeneration in the Adult CNS
Injuries to the adult central nervous system (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).
Gabapentinoids such as gabapentin and PGB also improved functional recovery in mice and neurological function in SCI patients. Thus, our findings suggest that targeting Alpha2delta2 may be a novel treatment strategy to promote structural plasticity and regeneration following human CNS trauma.
