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Cited by 314Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroscience and Neuropharmacology Research

GSK-3 and tau: a key duet in Alzheimer’s disease

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Sayas, Carmen Laura, Ávila, Jesús·2021·Cells
DOI 10.3390/cells10040721PMC PMC8063930
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Abstract

Glycogen synthase kinase-3 (GSK-3) is a ubiquitously expressed serine/threonine kinase with a plethora of substrates. As a modulator of several cellular processes, GSK-3 has a central position in cell metabolism and signaling, with important roles both in physiological and pathological conditions. GSK-3 has been associated with a number of human disorders, such as neurodegenerative diseases including Alzheimer's disease (AD). GSK-3 contributes to the hyperphosphorylation of tau protein, the main component of neurofibrillary tangles (NFTs), one of the hallmarks of AD. GSK-3 is further involved in the regulation of different neuronal processes that are dysregulated during AD pathogenesis, such as the generation of amyloid-β (Aβ) peptide or Aβ-induced cell death, axonal transport, cholinergic function, and adult neurogenesis or synaptic function. In this review, we will summarize recent data about GSK-3 involvement in these processes contributing to AD pathology, mostly focusing on the crucial interplay between GSK-3 and tau protein. We further discuss the current development of potential AD therapies targeting GSK-3 or GSK-3-phosphorylated tau.

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  • Interaction of SGK1, GSK-3β, and Tau leads to formation of an SGK1-GSK-3β-Tau complex, contributing to abnormal Tau tangles and disintegrating microtubules in neurons.

    “Interaction of these proteins lead to the formation of an SGK1-GSK-3β-Tau complex, contributing to abnormal Tau tangles and ultimately resulting in disintegrating microtubules in neurons”

    From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Sayas and Avila, 2021

    Section 3 reports a tau–GSK-3β complex and links tau phosphorylation to reduced microtubule binding and neurofibrillary tangles. It does not identify SGK1 as part of that complex or establish the claimed sequence ending in disintegrating neuronal microtubules (searched for SGK1 and the three-protein complex). (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Sayas, C. L., & Ávila, J.
Affiliations
  • Universidad de La Laguna (ES)
  • Consejo Superior de Investigaciones Científicas (ES)
Corresponding author
  • Sayas, Carmen Laura
  • Ávila, Jesús
ORCID
Venue
Cells
Publisher
MDPI AG
Published
2021-03-24
Volume
10
Issue
4
Pages
721
ISSN
2073-4409 (ISSN-L)
DOI
10.3390/cells10040721
PMC
PMC8063930
OpenAlex
W3138760932
Cited by
314
References
20
Citations by year
2026: 67 · 2025: 89 · 2024: 67 · 2023: 43 · 2022: 33 · 2021: 15
FWCI
5.30
Type
journal article
Language
en
Open access
Licence
Locations
  • Cells (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by-nc)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Universidad de La Laguna
  • Ministerio de Economía y Competitividad (PGC-2018-09177-B-100)
  • Cabildo de Tenerife
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
glycogen synthase kinase-3, tau protein, Alzheimer's disease, tau hyperphosphorylation, neurofibrillary tangles, amyloid-beta, axonal transport, cholinergic activity, adult neurogenesis, synaptic function, GSK-3 inhibitors, neurodegeneration
MeSH terms
Alzheimer Disease, Axonal Transport, Cognition, Humans, tau Proteins, Glycogen Synthase Kinase 3, Neurogenesis

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