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Cited by 158Alzheimer's disease research and treatmentsHeavy Metal Exposure and ToxicityMetal complexes synthesis and properties

Minding metals: Tailoring multifunctional chelating agents for neurodegenerative disease

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Perez, Lissette R., Franz, Katherine J.·2010·Dalton Trans.
DOI 10.1039/b919237aPMC PMC2860397
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Abstract

Neurodegenerative diseases like Alzheimer's and Parkinson's disease are associated with elevated levels of iron, copper, and zinc and consequentially high levels of oxidative stress. Given the multifactorial nature of these diseases, it is becoming evident that the next generation of therapies must have multiple functions to combat multiple mechanisms of disease progression. Metal-chelating agents provide one such function as an intervention for ameliorating metal-associated damage in degenerative diseases. Targeting chelators to adjust localized metal imbalances in the brain, however, presents significant challenges. In this perspective, we focus on some noteworthy advances in the area of multifunctional metal chelators as potential therapeutic agents for neurodegenerative diseases. In addition to metal chelating ability, these agents also contain features designed to improve their uptake across the blood-brain barrier, increase their selectivity for metals in damage-prone environments, increase antioxidant capabilities, lower Abeta peptide aggregation, or inhibit disease-associated enzymes such as monoamine oxidase and acetylcholinesterase.

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  • Two approaches have been pursued in BFC design: direct incorporation of metal-binding atom donors into the structural framework of an Aβ-interacting compound, and linking the metal-chelating and Aβ-binding molecular fragments.

    “In this context, two approaches have been pursued in BFC design. 31,49–58 One strategy is based on the direct incorporation of metal-binding atom donors into the structural framework of an Aβ-interacting compoud (Scheme 1, approach A), and the other involves linking the metal-chelating and Aβ-binding molecular fragments (Scheme 1, approach B).”

    From Bifunctional Compounds for Controlling Metal-Mediated Aggregation of the Aβ<sub>42</sub>Peptide (2012) · cites this paper as [50]

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Authors
Perez, L. R., & Franz, K. J.
Affiliations
Duke University (US)
Corresponding author
Franz, Katherine J.
ORCID
Franz, Katherine J.
Venue
Dalton Trans.
Publisher
Royal Society of Chemistry (RSC)
Published
2010
Volume
39
Issue
9
Pages
2177-2187
ISSN
  • 1477-9226 (ISSN-L)
  • 1477-9234
DOI
10.1039/b919237a
PMC
PMC2860397
OpenAlex
W2017578362
Cited by
156
References
89
Citations by year
2026: 2 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 7 · 2021: 4 · 2020: 5 · 2019: 6 · 2018: 10 · 2017: 10 · 2016: 10 · 2015: 10 · 2014: 8 · 2013: 16 · 2012: 24
FWCI
11.30
Type
journal article
Language
en
Open access
Locations
  • Dalton Transactions (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • DukeSpace (Duke University) (submittedVersion, cc-by-nc-nd)
Funders
  • Alfred P. Sloan Foundation
  • Camille and Henry Dreyfus Foundation
  • National Eye Institute (EY018922, R21EY018922)
  • National Institute of General Medical Sciences (R01GM084176, GM084176))
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
  • Health Sciences › Medicine › Oncology › Metal complexes synthesis and properties
Keywords
chelating agents, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, oxidative stress, iron, copper, zinc, blood-brain barrier, antioxidant activity, amyloid-beta aggregation, monoamine oxidase inhibition, acetylcholinesterase inhibition
MeSH terms
Chelating Agents, Humans, Metals, Neurodegenerative Diseases

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