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Cited by 12Alzheimer's disease research and treatmentsTrace Elements in HealthHeavy Metal Exposure and Toxicity

Targeting Metal Homeostasis as a Therapeutic Strategy for Alzheimer’s Disease

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Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy, Vilella, Antonietta, Daini, Eleonora, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy, De Benedictis, Chiara A., Cellular Neurobiology and Neuro-Nanotechnology Lab, Department of Biological Sciences, University of Limerick, Limerick, Ireland, Grabrucker, Andreas M., Cellular Neurobiology and Neuro-Nanotechnology Lab, Department of Biological Sciences, University of Limerick, Limerick, Ireland +2 more·2020·Alzheimer’s Disease: Drug Discovery
DOI 10.36255/exonpublications.alzheimersdisease.2020.ch5
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Abstract

Trace metals play an important role in the pathophysiology of amyloid precursor protein, amyloid beta, and tau, the key molecules involved in Alzheimer’s disease. Altering trace metal concentrations in the brain has been explored as a therapeutic strategy for Alzheimer’s disease. It is not only the accumulation of metals that drives amyloid beta aggregation, but also the lack of sufficient trace metals for other biological processes created through sequestration by amyloid beta that affects brain health and function. Thus, balancing metal levels to achieve therapeutic effects is an intricate process. This chapter summarizes the role of trace metals in Alzheimer’s disease and highlights the preclinical and clinical studies targeting metal homeostasis in animal models and humans. It further discusses recent developments in pharmacological approaches targeting metals in Alzheimer’s disease and provides an outlook on possible future treatments based on current translational research, for example, nanomedicine.

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  • Chelating agents clioquinol and deferoxamine reduce metal burden but face challenges related to BBB penetration, specificity, and systemic toxicity.

    “Chelating agents such as clioquinol and deferoxamine reduce metal burden but face challenges related to BBB penetration, specificity, and systemic toxicity [113].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [113]

    In “Targeted Interventions: Delivery of Metal-Attenuating Compounds” (page unavailable), the paper reports reduced Aβ burden with clioquinol and deferoxamine, and poor BBB penetration and systemic metal depletion with deferoxamine. It says clioquinol freely crosses the BBB and reports no adverse effects in treated mice, so those challenges cannot be applied to both agents. It does not establish that both reduce a measured metal burden or face a specificity problem. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The development of next-generation metal modulators that balance bioavailability with safety represents a promising but as yet unrealized avenue for disease modification.

    “The development of next-generation metal modulators that balance bioavailability with safety represents a promising but as yet unrealized avenue for disease modification [113].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [113]

  • MPACs are designed to modulate metal-Aβ interactions without causing systemic depletion.

    “More recent approaches focus on metal–protein attenuating compounds (MPACs) designed to modulate metal–Aβ interactions without causing systemic depletion [113].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [113]

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Cited by

Sorted by citations

Authors
Department of Biomedical, M. A. N. S., Vilella, A., Daini, E., Department of Biomedical, M. A. N. S., De Benedictis, C. A., Cellular Neurobiology and Neuro-Nanotechnology Lab, D. O. B. S., Grabrucker, A. M., Cellular Neurobiology and Neuro-Nanotechnology Lab, D. O. B. S., Bernal Institute, U. O. L., & Health Research Institute (HRI), U. O. L.
Affiliations
  • University of Modena and Reggio Emilia (IT)
  • University of Limerick (IE)
ORCID
Venue
Alzheimer’s Disease: Drug Discovery
Publisher
Exon Publications
Published
2020-12-18
Pages
83-98
DOI
10.36255/exonpublications.alzheimersdisease.2020.ch5
OpenAlex
W3117553870
Cited by
12
References
8
Citations by year
2026: 3 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 2
FWCI
5.22
Type
book chapter
Language
en
Open access
Licence
cc-by-nc
Locations
  • Exon Publications eBooks (publishedVersion, cc-by-nc)
  • IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
  • INFM-OAR (INFN Catania) (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
Keywords
Alzheimer's disease, metal homeostasis, trace metals, amyloid-beta, amyloid precursor protein, tau protein, metal sequestration, amyloid-beta aggregation, nanomedicine, animal models, clinical trials

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