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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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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DOI: https://doi.org/10.1007/s12035-013-8571-y