Control of neuronal ion channel function by glycogen synthase kinase-3: new prospective for an old kinase
Glycogen synthase kinase 3 (GSK-3) is an evolutionarily conserved multifaceted ubiquitous enzyme. In the central nervous system (CNS), GSK-3 acts through an intricate network of intracellular signaling pathways culminating in a highly divergent cascade of phosphorylations that control neuronal funct...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2012-07-01
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| Series: | Frontiers in Molecular Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnmol.2012.00080/full |
| _version_ | 1818390888151252992 |
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| author | Norelle Christine Wildburger Norelle Christine Wildburger Norelle Christine Wildburger Fernanda eLaezza Fernanda eLaezza Fernanda eLaezza |
| author_facet | Norelle Christine Wildburger Norelle Christine Wildburger Norelle Christine Wildburger Fernanda eLaezza Fernanda eLaezza Fernanda eLaezza |
| author_sort | Norelle Christine Wildburger |
| collection | DOAJ |
| description | Glycogen synthase kinase 3 (GSK-3) is an evolutionarily conserved multifaceted ubiquitous enzyme. In the central nervous system (CNS), GSK-3 acts through an intricate network of intracellular signaling pathways culminating in a highly divergent cascade of phosphorylations that control neuronal function during development and adulthood. Accumulated evidence indicates that altered levels of GSK-3 correlate with maladaptive plasticity of neuronal circuitries in psychiatric disorders, addictive behaviors, and neurodegenerative diseases, and pharmacological interventions known to limit GSK-3 can counteract some of these deficits. Thus, targeting the GSK-3 cascade for therapeutic interventions against this broad spectrum of brain diseases has raised a tremendous interest. Yet, the multitude of GSK-3 downstream effectors poses a substantial challenge in the development of selective and potent medications that could efficiently block or modulate the activity of this enzyme. Although the full range of GSK-3 molecular targets are far from resolved, exciting new evidence indicates that ion channels regulating excitability, neurotransmitter release, and synaptic transmission, which ultimately contribute to the mechanisms underling brain plasticity and higher level cognitive and emotional processing, are new promising targets of this enzyme. Here, we will revise this new emerging role of GSK-3 in controlling the activity of voltage-gated Na+, K+, Ca2+ channels and ligand-gated glutamate receptors with the goal of highlighting new relevant endpoints of the neuronal GSK-3 cascade that could provide a platform for a better understanding of the mechanisms underlying the dysfunction of this kinase in the CNS and serve as a guidance for medication development against the broad range of GSK-3-linked human diseases. |
| first_indexed | 2024-12-14T05:04:47Z |
| format | Article |
| id | doaj.art-aa90a5fbec654ba2b3c7efb918f5c511 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-14T05:04:47Z |
| publishDate | 2012-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-aa90a5fbec654ba2b3c7efb918f5c5112022-12-21T23:16:09ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992012-07-01510.3389/fnmol.2012.0008027652Control of neuronal ion channel function by glycogen synthase kinase-3: new prospective for an old kinaseNorelle Christine Wildburger0Norelle Christine Wildburger1Norelle Christine Wildburger2Fernanda eLaezza3Fernanda eLaezza4Fernanda eLaezza5The University of Texas Medical BranchThe University of Texas Medical BranchThe University of Texas Medical BranchThe University of Texas Medical BranchThe University of Texas Medical BranchThe University of Texas Medical Branch Glycogen synthase kinase 3 (GSK-3) is an evolutionarily conserved multifaceted ubiquitous enzyme. In the central nervous system (CNS), GSK-3 acts through an intricate network of intracellular signaling pathways culminating in a highly divergent cascade of phosphorylations that control neuronal function during development and adulthood. Accumulated evidence indicates that altered levels of GSK-3 correlate with maladaptive plasticity of neuronal circuitries in psychiatric disorders, addictive behaviors, and neurodegenerative diseases, and pharmacological interventions known to limit GSK-3 can counteract some of these deficits. Thus, targeting the GSK-3 cascade for therapeutic interventions against this broad spectrum of brain diseases has raised a tremendous interest. Yet, the multitude of GSK-3 downstream effectors poses a substantial challenge in the development of selective and potent medications that could efficiently block or modulate the activity of this enzyme. Although the full range of GSK-3 molecular targets are far from resolved, exciting new evidence indicates that ion channels regulating excitability, neurotransmitter release, and synaptic transmission, which ultimately contribute to the mechanisms underling brain plasticity and higher level cognitive and emotional processing, are new promising targets of this enzyme. Here, we will revise this new emerging role of GSK-3 in controlling the activity of voltage-gated Na+, K+, Ca2+ channels and ligand-gated glutamate receptors with the goal of highlighting new relevant endpoints of the neuronal GSK-3 cascade that could provide a platform for a better understanding of the mechanisms underlying the dysfunction of this kinase in the CNS and serve as a guidance for medication development against the broad range of GSK-3-linked human diseases.http://journal.frontiersin.org/Journal/10.3389/fnmol.2012.00080/fullSynaptic Transmissionexcitabilityglutamate receptorssignalingkinasesneurotransmitter release |
| spellingShingle | Norelle Christine Wildburger Norelle Christine Wildburger Norelle Christine Wildburger Fernanda eLaezza Fernanda eLaezza Fernanda eLaezza Control of neuronal ion channel function by glycogen synthase kinase-3: new prospective for an old kinase Frontiers in Molecular Neuroscience Synaptic Transmission excitability glutamate receptors signaling kinases neurotransmitter release |
| title | Control of neuronal ion channel function by glycogen synthase kinase-3: new prospective for an old kinase |
| title_full | Control of neuronal ion channel function by glycogen synthase kinase-3: new prospective for an old kinase |
| title_fullStr | Control of neuronal ion channel function by glycogen synthase kinase-3: new prospective for an old kinase |
| title_full_unstemmed | Control of neuronal ion channel function by glycogen synthase kinase-3: new prospective for an old kinase |
| title_short | Control of neuronal ion channel function by glycogen synthase kinase-3: new prospective for an old kinase |
| title_sort | control of neuronal ion channel function by glycogen synthase kinase 3 new prospective for an old kinase |
| topic | Synaptic Transmission excitability glutamate receptors signaling kinases neurotransmitter release |
| url | http://journal.frontiersin.org/Journal/10.3389/fnmol.2012.00080/full |
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