The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
New Insights on How Metals Disrupt Amyloid β-Aggregation and Their Effects on Amyloid-β Cytotoxicity
Open accessAbstract
Amyloid-beta protein (A beta) aggregates in the brain to form senile plaques. By using thioflavin T, a dye that specifically binds to fibrillar structures, we found that metals such as Zn(II) and Cu(II) normally inhibit amyloid beta-aggregation. Another method for detecting A beta, which does not distinguish the types of aggregates, showed that these metals induce a non-beta-sheeted aggregation, as reported previously. Secondary structural analysis and microscopic studies revealed that metals induced A beta to make non-fibrillar aggregates by disrupting beta-sheet formation. These non-fibrillar A beta aggregates displayed much weaker Congo Red birefringence, and in separate cell culture experiments, were less toxic than self beta-aggregates, as demonstrated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. The toxicity of soluble A beta was enhanced in the presence of Cu(II), which suggests the previously hypothesized role of A beta in generating oxidative stress. Finally, under an acidic condition, similar to that in the inflammation associated with senile plaques, beta-aggregation was robustly facilitated at one specific concentration of Zn(II) in the presence of heparin. However, because a higher concentration of Zn(II) virtually abolished this abnormal phenomenon, and at normal pH any concentrations strongly inhibit beta-aggregation and its associated cytotoxicity, including its anti-oxidative nature we suggest that Zn(II) has an overall protective ef…
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“However, the role of metal ions in Aβ42 aggregation still remains unclear and only few reports are available in the literature.37–41”
From Bifunctional Compounds for Controlling Metal-Mediated Aggregation of the Aβ42Peptide (2012) · cites this paper as [39]
In the citing paper
“Cu2+ was shown to reduce Aβ42 aggregation.39,40”
From Bifunctional Compounds for Controlling Metal-Mediated Aggregation of the Aβ42Peptide (2012) · cites this paper as [39]
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Metadata
- Authors
- Yoshiike, Y., Tanemura, K., Murayama, O., Akagi, T., Murayama, M., Sato, S., Sun, X., Tanaka, N., & Takashima, A.
- Affiliations
- Tokyo Institute of Technology (JP)
- RIKEN Center for Brain Science (JP)
- Corresponding author
- Takashima, Akihiko
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-08
- Volume
- 276
- Issue
- 34
- Pages
- 32293-32299
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2081099437
- Cited by
- 244
- References
- 60
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 5 · 2021: 6 · 2020: 8 · 2019: 12 · 2018: 9 · 2017: 11 · 2016: 6 · 2015: 6 · 2014: 12 · 2013: 9 · 2012: 22
- FWCI
- 4.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- amyloid-beta, metal-induced aggregation, zinc, copper, amyloid cytotoxicity, oxidative stress, amyloid plaques, heparin, pH effect, Alzheimer's disease
- MeSH terms
- Animals, Cell Line, Cell Survival, Cells, Cultured, Circular Dichroism, Copper, Hippocampus, Humans, Neurons, Zinc, Amyloid beta-Peptides, Cell Death, Rats
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