Control of neuronal excitability by GSK-3beta: epilepsy and beyond.
Open accessAbstract
Glycogen synthase kinase 3beta (GSK-3β) is an enzyme with a variety of cellular functions in addition to the regulation of glycogen metabolism. In the central nervous system, different intracellular signaling pathways converge on GSK-3β through a cascade of phosphorylation events that ultimately control a broad range of neuronal functions in the development and adulthood. In mice, genetically removing or increasing GSK-3β cause distinct functional and structural neuronal phenotypes and consequently affect cognition. Precise control of GSK-3β activity is important for such processes as neuronal migration, development of neuronal morphology, synaptic plasticity, excitability, and gene expression. Altered GSK-3β activity contributes to aberrant plasticity within neuronal circuits leading to neurological, psychiatric disorders, and neurodegenerative diseases. Therapeutically targeting GSK-3β can restore the aberrant plasticity of neuronal networks at least in animal models of these diseases. Although the complete repertoire of GSK-3β neuronal substrates has not been defined, emerging evidence shows that different ion channels and their accessory proteins controlling excitability, neurotransmitter release, and synaptic transmission are regulated by GSK-3β, thereby supporting mechanisms of synaptic plasticity in cognition. Dysregulation of ion channel function by defective GSK-3β activity sustains abnormal excitability in the development of epilepsy and other GSK-3β-linked human diseases.
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Both GSK-3β and CDK5 play a role in neuronal excitability through involvement in GABAergic and glutamatergic neurotransmission.
“Both GSK-3β and CDK5 play a role in neuronal excitability through involvement in GABAergic and glutamatergic neurotransmission, and inhibiting their activity can affect network activity through various mechanisms (Sen et al., 2008; Jaworski, 2020; Toral-Rios et al., 2020; Banerjee et al., 2021).”
From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Jaworski, 2020
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Sorted by citations
Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms
Hwang, K., Vaknalli, R. N., Addo-Osafo, K., Vicente, M., & Vossel, K. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.903973 · Cited by 35 · see citing works
“Both GSK-3β and CDK5 play a role in neuronal excitability through involvement in GABAergic and glutamatergic neurotransmission, and inhibiting their activity can affect network activity through various mechanisms (Sen et al., 2008; Jaworski, 2020; Toral-Rios et al., 2020; Banerjee et al., 2021).”
Background
- Authors
- Jaworski, T.
- Affiliations
- Instytut Biologii Doświadczalnej im. Marcelego Nenckiego (PL)
- Corresponding author
- Jaworski, Tomasz
- ORCID
- Jaworski, Tomasz
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 1867
- Issue
- 9
- Pages
- 118745
- ISSN
- 0167-4889 (ISSN-L)
- OpenAlex
- W3027815523
- Cited by
- 43
- References
- 11
- Citations by year
- 2026: 4 · 2025: 14 · 2024: 5 · 2023: 4 · 2022: 12 · 2021: 4
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Narodowe Centrum Nauki
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- GSK3β, neuronal excitability, epilepsy, ion channels, synaptic plasticity, phosphorylation, neurotransmitter release, synaptic transmission, neurodegenerative diseases, mental illness, cognitive function, neuronal development, GSK-3β inhibitors
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Drug Development, Animals, Brain, Disease Models, Animal, Disease Susceptibility, Epilepsy, Humans, Ion Channels, Neurons, Signal Transduction, Electrophysiological Phenomena, Brain Waves, Molecular Targeted Therapy
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