Cited by 159Alzheimer's disease research and treatmentsEpilepsy research and treatmentDementia and Cognitive Impairment Research

GSK3β and tau protein in Alzheimer's disease and epilepsy

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Toral-Rios, Danira, Pichardo-Rojas, Pavel S., Alonso-Vanegas, Mario, Campos-Peña, Victoria·2020·Frontiers in Cellular Neuroscience

Abstract

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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Registry

Crossref · 10.3389/fncel.2020.00019

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87 of 87 references verified0 citation errors · 0 not checkable

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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 measured
  • Glycogen 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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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
Published
2020-03-17
Volume
14
Pages
19-19
ISSN
1662-5102 (ISSN-L)
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
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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