Cited by 111Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchTrace Elements in Health

Zinc Binding to Amyloid-β: Isothermal Titration Calorimetry and Zn Competition Experiments with Zn Sensors

Talmard, Christine, Bouzan, Anaïs, Faller, Peter·2007·Biochemistry

Abstract

Aggregation of the peptide amyloid-beta (Abeta) to amyloid plaques is a key event in Alzheimer's disease. According to the amyloid cascade hypothesis, Abeta aggregates are toxic to neurons via the production of reactive oxygen species and are hence directly involved in the cause of the disease. Zinc ions play an important role, because they are able to bind to Abeta and influence the aggregation properties. In the present work isothermal titration calorimetry and Zn sensors (zincon, Newport Green, and zinquin) were used to investigate the interaction of Zn with the full-length Abeta1-40 and Abeta1-42, as well as the truncated Abeta1-16 and Abeta1-28. The results suggest that Zn binding to Abeta induces a release of approximately 0.9 proton by the peptide. This correspond to the expected value upon Zn binding to the three histidines and indicates that further ligands are not deprotonated upon Zn binding. Such behavior is expected for carboxylates, but not the N-terminus. Moreover, the apparent dissociation constant (Kd,app) of Zn binding to all forms of Abeta is in the low micromolar range (1-20 microM) and rather independent of the aggregation state including soluble Abeta, Abeta fibrils, or Zn-induced Abeta aggregates. Finally, Zn in the soluble or aggregated Zn-Abeta form is well accessible for Zn chelators. The potential repercussions on metal chelation therapy are discussed.

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Crossref · 10.1021/bi701355j

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Authors
Talmard, C., Bouzan, A., & Faller, P.
Affiliations
Centre National de la Recherche Scientifique (FR)
Corresponding author
Faller, Peter
Venue
Biochemistry
Published
2007-11-01
Volume
46
Issue
47
Pages
13658-13666
ISSN
  • 0006-2960 (ISSN-L)
  • 1520-4995
OpenAlex
W2071713054
Cited by
111
References
26
Citations by year
2025: 5 · 2024: 2 · 2023: 4 · 2022: 6 · 2021: 1 · 2020: 4 · 2019: 6 · 2018: 9 · 2017: 7 · 2016: 3 · 2015: 4 · 2014: 4 · 2013: 10 · 2012: 14
FWCI
5.57
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Keywords
amyloid-beta, zinc binding, Alzheimer's disease, chelation therapy, zincon, Aβ40, amyloid-beta 42, proton release, histidine ligands, dissociation constant, metal-induced aggregation, metal chelators
MeSH terms
Alzheimer Disease, Binding Sites, Calorimetry, Kinetics, Peptide Fragments, Temperature, Thermodynamics, Zinc, Amyloid beta-Peptides

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