Cited by 110Alzheimer's disease research and treatmentsCholinesterase and Neurodegenerative DiseasesComputational Drug Discovery Methods

Glycogen Synthase Kinase 3β: A New Gold Rush in Anti-Alzheimer’s Disease Multitarget Drug Discovery?: Miniperspective

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De Simone, Angela, Tumiatti, Vincenzo, Andrisano, Vincenza, Milelli, Andrea·2021·Journal of Medicinal Chemistry

Abstract

Alzheimer's disease (AD), like other multifactorial diseases, is the result of a systemic breakdown of different physiological networks. As result, several lines of evidence suggest that it could be more efficiently tackled by molecules directed toward different dysregulated biochemical targets or pathways. In this context, the selection of targets to which the new molecules will be directed is crucial. For years, the design of such multitarget-directed ligands (MTDLs) has been based on the selection of main targets involved in the "cholinergic" and the "β-amyloid" hypothesis. Recently, there have been some reports on MTDLs targeting the glycogen synthase kinase 3β (GSK-3β) enzyme, due to its appealing properties. Indeed, this enzyme is involved in tau hyperphosphorylation, controls a multitude of CNS-specific signaling pathways, and establishes strict connections with several factors implicated in AD pathogenesis. In the present Miniperspective, we will discuss the reasons behind the development of GSK-3β-directed MTDLs and highlight some of the recent efforts to obtain these new classes of MTDLs as potential disease-modifying agents.

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  • BACE-1 and GSK-3β inhibition are being studied as possible targets for Alzheimer's disease.

    “Nowadays, other possible targets are being studied, such as beta-secretase 1 (BACE-1) and glycogen synthase kinase-3β (GSK-3β) inhibition (De Simone et al., 2021;Prati et al., 2015).”

    From Multi-target neuroprotective effects of herbal medicines for Alzheimer's disease (2022) · cites this paper as De Simone et al., 2021

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Authors
De Simone, A., Tumiatti, V., Andrisano, V., & Milelli, A.
Affiliations
  • Department of Drug Science and Technology, University of Turin, Via Giuria 9, 10125 Torino, Italy
  • University of Bologna (IT)
Corresponding author
Milelli, Andrea
Venue
Journal of Medicinal Chemistry
Published
2020-12-21
Volume
64
Issue
1
Pages
26-41
ISSN
  • 0022-2623 (ISSN-L)
  • 1520-4804
OpenAlex
W3113759919
Cited by
110
References
156
Citations by year
2026: 15 · 2025: 32 · 2024: 19 · 2023: 15 · 2022: 22 · 2021: 7
FWCI
7.22
Type
journal article
Language
en
Open access
Locations
  • Journal of Medicinal Chemistry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
Funders
Universit? di Bologna
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
  • Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
Keywords
glycogen synthase kinase-3β, multi-target-directed ligands, Alzheimer's disease, tau hyperphosphorylation, disease-modifying drugs, GSK-3β inhibitors, cholinergic hypothesis, amyloid hypothesis
MeSH terms
Glycogen Synthase Kinase 3 beta, Alzheimer Disease, Humans, Phosphorylation, Drug Discovery

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