Journal Article

DZNE-2020-05179

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The Calcium Channel Subunit Alpha2delta2 Suppresses Axon Regeneration in the Adult CNS.

Tedeschi, A. (First author)DZNE* ; Dupraz, S.DZNE* ; Laskowski, C. J.DZNE* ; Xue, J. ; Ulas, T. ; Beyer, M. ; Schultze, J. L.DZNE* ; Bradke, F. (Last author)DZNE*

2016
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.neuron.2016.09.026

Abstract: 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.

Keyword(s): Animals (MeSH) ; Axons: drug effects (MeSH) ; Axons: physiology (MeSH) ; Calcium Channel Blockers: pharmacology (MeSH) ; Calcium Channels: drug effects (MeSH) ; Calcium Channels: genetics (MeSH) ; Calcium Channels: metabolism (MeSH) ; Central Nervous System (MeSH) ; Female (MeSH) ; Ganglia, Spinal: cytology (MeSH) ; Ganglia, Spinal: metabolism (MeSH) ; Gene Expression Profiling (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Knockout (MeSH) ; Neuronal Outgrowth: drug effects (MeSH) ; Neuronal Outgrowth: genetics (MeSH) ; Neurons: metabolism (MeSH) ; Pregabalin: pharmacology (MeSH) ; RNA, Messenger: metabolism (MeSH) ; Regeneration: drug effects (MeSH) ; Regeneration: genetics (MeSH) ; Sequence Analysis, RNA (MeSH) ; Spinal Cord Injuries: metabolism (MeSH) ; Cacna2d2 protein, mouse ; Calcium Channel Blockers ; Calcium Channels ; RNA, Messenger ; Pregabalin

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Contributing Institute(s):

1. Axon Growth and Regeneration (AG Bradke)
2. Platform for Single Cell Genomics and Epigenomics (Schultze - PRECISE)

Research Program(s):

1. 341 - Molecular Signaling (POF3-341) (POF3-341)
2. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Experiment(s):

1. Platform for Single Cell Genomics and Epigenomics at DZNE University of Bonn

Appears in the scientific report 2016

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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