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

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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.

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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

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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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  1. Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), University of Barcelona, Baldiri Reixac 15-21, 08028, Barcelona, Spain

    Oscar Seira & José Antonio del Río

  2. Department of Cell Biology, Faculty of Biology, Diagonal 643, University of Barcelona, 08028, Barcelona, Spain

    Oscar Seira & José Antonio del Río

  3. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (Ciberned), 08028, Barcelona, Spain

    Oscar Seira & José Antonio del Río

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Seira, O., del Río, J.A. Glycogen Synthase Kinase 3 Beta (GSK3β) at the Tip of Neuronal Development and Regeneration. Mol Neurobiol 49, 931–944 (2014). https://doi.org/10.1007/s12035-013-8571-y

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