GSK3β and tau protein in Alzheimer's disease and epilepsy
Open accessAbstract
Alzheimer's disease (AD) is the most common form of dementia present in older adults; its etiology involves genetic and environmental factors. In recent years, epidemiological studies have shown a correlation between AD and chronic epilepsy since a considerable number of patients with AD may present seizures later on. Although the pathophysiology of seizures in AD is not completely understood, it could represent the result of several molecular mechanisms linked to amyloid beta-peptide (Aβ) accumulation and the hyperphosphorylation of tau protein, which may induce an imbalance in the release and recapture of excitatory and inhibitory neurotransmitters, structural alterations of the neuronal cytoskeleton, synaptic loss, and neuroinflammation. These changes could favor the recurrent development of hypersynchronous discharges and epileptogenesis, which, in a chronic state, favor the neurodegenerative process and influence the cognitive decline observed in AD. Supporting this correlation, histopathological studies in the brain tissue of temporal lobe epilepsy (TLE) patients have revealed the presence of Aβ deposits and the accumulation of tau protein in the neurofibrillary tangles (NFTs), accompanied by an increase of glycogen synthase kinase-3 beta (GSK3β) activity that may lead to an imminent alteration in posttranslational modifications of some microtubule-associated proteins (MAPs), mainly tau. The present review is focused on understanding the pathological aspects of GSK3β and tau in the development of TLE and AD.
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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 Toral-Rios et al., 2020
The “GSK3β and Epilepsy” section links GSK3β to hyperexcitability through NMDA and glutamate AMPA receptors, and reports anticonvulsant activity from GSK3β inhibition (page not provided). The “Therapeutics” section mentions CDK5 as a tau kinase, but our copy does not link CDK5 to neuronal excitability or either kinase to GABAergic neurotransmission. (LLM, conf=0.87)
Experimental — accuracy not yet measuredGlycogen synthase kinase-3β is a relevant kinase responsible for tau phosphorylation.
“One relevant kinase responsible for tau phosphorylation is glycogen synthase kinase-3β (GSK-3β) (Toral-Rios et al., 2020).”
From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Toral-Rios et al., 2020
Increased GSK-3β activity induces Aβ deposition extracellularly.
“Furthermore, increased GSK-3β activity also induces Aβ deposition extracellularly (Griebel et al., 2019;Toral-Rios et al., 2020).”
From Multi-target neuroprotective effects of herbal medicines for Alzheimer's disease (2022) · cites this paper as Toral-Rios et al., 2020
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Protein Homeostasis Networks and the Use of Yeast to Guide Interventions in Alzheimer’s Disease
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Oat Extract Avenanthramide-C Reverses Hippocampal Long-Term Potentiation Decline in Tg2576 Mice
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Mechanisms of Phytoremediation by Resveratrol against Cadmium Toxicity
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The Inflammation-Induced Dysregulation of Reelin Homeostasis Hypothesis of Alzheimer’s Disease
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RhoA/ROCK/GSK3β Signaling: A Keystone in Understanding Alzheimer’s Disease
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mRNA and circRNA mislocalization to synapses are key features of Alzheimer’s disease
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Zebrafish metabolomics: a comprehensive approach to understanding health and disease
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Investigation of Potential Drug Targets for Cholesterol Regulation to Treat Alzheimer’s Disease
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The Association Between Alzheimer's Disease and Epilepsy: A Narrative Review
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Dendrobine Ameliorates Alzheimer’s Disease-like Pathology and Cognitive Decline in 3 × Tg-AD Mice
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Molecular and Biochemical Pathways Encompassing Diabetes Mellitus and Dementia
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Huang, X., Li, T., Zhou, L., Liu, T., Xiong, L., & Yu, C. (2021) · Ibrain · doi:10.1002/j.2769-2795.2021.tb00060.x · Cited by 11 · see citing works
GSK3 Is a Central Player in Retinal Degenerative Diseases but a Challenging Therapeutic Target
Hottin, C., Perron, M., & Roger, J. E. (2022) · Cells · doi:10.3390/cells11182898 · Cited by 9 · see citing works
Tauopathies: Emerging discoveries on tau protein, with a special focus on Alzheimer's disease
Hattiholi, A., Hegde, H., & Shetty, S. K. (2025) · Neuropeptides · doi:10.1016/j.npep.2025.102536 · Cited by 10 · see citing works
Regulation of eukaryotic protein kinases by Pin1, a peptidyl-prolyl isomerase
Chen, X., & Igumenova, T. I. (2022) · Advances in Biological Regulation · doi:10.1016/j.jbior.2022.100938 · Cited by 8 · see citing works
Pragati, & Sarkar, S. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03599-y · Cited by 8 · see citing works
Althobaiti, N. A., Al-Abbas, N. S., Alsharif, I., Albalawi, A. E., Almars, . I., Basabrain, A. A., Jafer, A., Ellatif, S. A. A., Bauthman, N. M., Almohaimeed, H. M., et al. (2024) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2024.167353 · Cited by 7 · see citing works
Masand, V. H., Al‐Hussain, S. A., Masand, G. S., Samad, A., Gawali, R. G., Jadhav, S., & Zaki, M. E. A. (2024) · Computational Biology and Chemistry · doi:10.1016/j.compbiolchem.2024.108324 · Cited by 7 · see citing works
- Authors
- Toral-Rios, D., Pichardo-Rojas, P. S., Alonso-Vanegas, M., & Campos-Peña, V.
- Affiliations
- Universidad Autónoma de Baja California (MX)
- Venue
- Frontiers in Cellular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2020-03-17
- Volume
- 14
- Pages
- 19-19
- ISSN
- 1662-5102 (ISSN-L)
- PMC
- PMC7089874
- OpenAlex
- W3012558556
- Cited by
- 158
- References
- 88
- Citations by year
- 2026: 18 · 2025: 28 · 2024: 35 · 2023: 31 · 2022: 25 · 2021: 15 · 2020: 6
- FWCI
- 11.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Greater South Information System
- Funders
- Consejo Nacional de Ciencia y Tecnología (S0008)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, epilepsy, temporal lobe epilepsy, GSK3β, tau protein, tau hyperphosphorylation, amyloid-beta, neurofibrillary tangles, epileptogenesis, seizures, neuroinflammation, synaptic loss, cognitive decline, microtubule-associated proteins
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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