TY  - JOUR
AU  - Tedeschi, Andrea
AU  - Dupraz, Sebastian
AU  - Laskowski, Claudia J
AU  - Xue, Jia
AU  - Ulas, Thomas
AU  - Beyer, Marc
AU  - Schultze, Joachim L
AU  - Bradke, Frank
TI  - The Calcium Channel Subunit Alpha2delta2 Suppresses Axon Regeneration in the Adult CNS.
JO  - Neuron
VL  - 92
IS  - 2
SN  - 0896-6273
CY  - New York, NY
PB  - Elsevier
M1  - DZNE-2020-05179
SP  - 419-434
PY  - 2016
AB  - 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.
KW  - Animals
KW  - Axons: drug effects
KW  - Axons: physiology
KW  - Calcium Channel Blockers: pharmacology
KW  - Calcium Channels: drug effects
KW  - Calcium Channels: genetics
KW  - Calcium Channels: metabolism
KW  - Central Nervous System
KW  - Female
KW  - Ganglia, Spinal: cytology
KW  - Ganglia, Spinal: metabolism
KW  - Gene Expression Profiling
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Mice, Knockout
KW  - Neuronal Outgrowth: drug effects
KW  - Neuronal Outgrowth: genetics
KW  - Neurons: metabolism
KW  - Pregabalin: pharmacology
KW  - RNA, Messenger: metabolism
KW  - Regeneration: drug effects
KW  - Regeneration: genetics
KW  - Sequence Analysis, RNA
KW  - Spinal Cord Injuries: metabolism
KW  - Cacna2d2 protein, mouse (NLM Chemicals)
KW  - Calcium Channel Blockers (NLM Chemicals)
KW  - Calcium Channels (NLM Chemicals)
KW  - RNA, Messenger (NLM Chemicals)
KW  - Pregabalin (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:27720483
DO  - DOI:10.1016/j.neuron.2016.09.026
UR  - https://pub.dzne.de/record/138857
ER  -