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Sustained GSK3 activity markedly facilitates nerve regeneration

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  • Philipp Gobrecht

    (Heinrich Heine University of Düsseldorf, Merowingerplatz 1a)

  • Marco Leibinger

    (Heinrich Heine University of Düsseldorf, Merowingerplatz 1a)

  • Anastasia Andreadaki

    (Heinrich Heine University of Düsseldorf, Merowingerplatz 1a)

  • Dietmar Fischer

    (Heinrich Heine University of Düsseldorf, Merowingerplatz 1a)

Abstract

Promotion of axonal growth of injured DRG neurons improves the functional recovery associated with peripheral nerve regeneration. Both isoforms of glycogen synthase kinase 3 (GSK3; α and β) are phosphorylated and inactivated via phosphatidylinositide 3-kinase (PI3K)/AKT signalling upon sciatic nerve crush (SNC). However, the role of GSK3 phosphorylation in this context is highly controversial. Here we use knock-in mice expressing GSK3 isoforms resistant to inhibitory PI3K/AKT phosphorylation, and unexpectedly find markedly accelerated axon growth of DRG neurons in culture and in vivo after SNC compared with controls. Moreover, this enhanced regeneration strikingly accelerates functional recovery after SNC. These effects are GSK3 activity dependent and associated with elevated MAP1B phosphorylation. Altogether, our data suggest that PI3K/AKT-mediated inhibitory phosphorylation of GSK3 limits the regenerative outcome after peripheral nerve injury. Therefore, suppression of this internal ‘regenerative break’ may potentially provide a new perspective for the clinical treatment of nerve injuries.

Suggested Citation

  • Philipp Gobrecht & Marco Leibinger & Anastasia Andreadaki & Dietmar Fischer, 2014. "Sustained GSK3 activity markedly facilitates nerve regeneration," Nature Communications, Nature, vol. 5(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5561
    DOI: 10.1038/ncomms5561
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    Cited by:

    1. Philipp Gobrecht & Daniel Terheyden-Keighley & Dietmar Fischer, 2019. "The Role of Microtubule Detyrosination in Axon Regeneration," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 17(1), pages 12447-12449, April.

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