Molecular Neurobiology

, Volume 49, Issue 2, pp 931–944 | Cite as

Glycogen Synthase Kinase 3 Beta (GSK3β) at the Tip of Neuronal Development and Regeneration

Article

Abstract

Gaining a basic understanding of the inhibitory molecules and the intracellular signaling involved in axon development and repulsion after neural lesions is of clear biomedical interest. In recent years, numerous studies have described new molecules and intracellular mechanisms that impair axonal outgrowth after injury. In this scenario, the role of glycogen synthase kinase 3 beta (GSK3β) in the axonal responses that occur after central nervous system (CNS) lesions began to be elucidated. GSK3β function in the nervous tissue is associated with neural development, neuron polarization, and, more recently, neurodegeneration. In fact, GSK3β has been considered as a putative therapeutic target for promoting functional recovery in injured or degenerative CNS. In this review, we summarize current understanding of the role of GSK3β during neuronal development and regeneration. In particular, we discuss GSK3β activity levels and their possible impact on cytoskeleton dynamics during both processes.

Keywords

Neuritogenesis Axonal injury Neurite outgrowth inhibition Microtubule-associated protein Actin cytoskeleton 

Abbreviations

APC

Adenomatous polyposis coli

BDNF

Brain-derived neurothrophic factor

Cdk5

Cyclin-dependent kinase 5

CGN

Cerebellar granule neuron

CLASP2

Cytoplasmic linker proteins (CLIP-associate protein)

CRMP

Collapsing response mediator protein

CSPG

Chondroitin sulfate proteoglycan

CST

Corticospinal tract

DRG

Dorsal root ganglion

DS

Dermatan

EGF

Epidermal growth factor

FGF

Fibroblast growth factor

GAG

Glycosaminoglycan

GSK3β

Glycogen synthase kinase 3 beta

HS

Heparan sulfate

ILK

Integrin-linked kinase

KS

Keratan sulfate

MAIs

Myelin-associated inhibitors

MAG

Myelin-associated glycoprotein

MAPs

Microtubule-associated proteins

MAPK

Mitogen-activated protein kinase

MTOC

Microtubule organization center

NgR1

Nogo receptor 1

NGF

Neural growth factor

Np

Neuropilin

NT-3

Neurotrophine-3

Olfm1

Olfactomedin1

OMgp

Oligodendrocyte myelin glycoprotein

PirB

Paired immunoglobuline-like receptor B

PI3K

Phosphoinositide 3-kinase

PKA

Protein kinase A

Plex

Plexin

PTEN

Phosphatase and tensin homolog

PTPase

Protein tyrosine phosphatase

PTPσ

Protein phosphatase 3

TOR

Target of rapamycin

VEGFr

Vascular endothelial growth factor receptor

ZAK1

Zipper sterile-motif kinase

Notes

Acknowledgments

The authors thank V. Gil and S. Nocentini for critical reading of the manuscript and Tom Yohannan for linguistic advice. This research was supported by the Seventh Framework Programme of the European Commission, grant agreement 222887, FP7-PRIORITY, and DEMTEST (Joint Programming of Neurodegenerative Diseases), the Spanish Ministry of Science and Innovation (BFU2012-32617), the Generalitat de Catalunya (SGR2009-366), La Caixa Obra Social Foundation (LCOSF), and the Instituto Salud Carlos III (PI11/03028). OS was supported by MICINN, IBEC (Strategic Research Initiative program founded by LCOSF) and ISCIII (Ciberned).

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC)University of BarcelonaBarcelonaSpain
  2. 2.Department of Cell Biology, Faculty of Biology, Diagonal 643University of BarcelonaBarcelonaSpain
  3. 3.Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (Ciberned)BarcelonaSpain

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