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The DOI matches its Crossref record, with a small difference in title or year; 26 of the 28 references it cites were found in a registry or an index.

Self-Assembly of Aβ 1 - 42 into Globular Neurotoxins

Chromy, Brett A., Nowak, Richard J., Lambert, Mary P., Viola, Kirsten L., Chang, Lei, Velasco, Pauline T., Jones, Bryan W., Fernandez, Sara J., Lacor, Pascale N., Horowitz, Peleg, Finch, Caleb E., Krafft, Grant A., Klein, William L.·2003·Biochemistry
DOI 10.1021/bi030029q
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Abstract

Amyloid beta 1-42 (Abeta(1-42)) is a self-associating peptide that becomes neurotoxic upon aggregation. Toxicity originally was attributed to the presence of large, readily formed Abeta fibrils, but a variety of other toxic species are now known. The current study shows that Abeta(1-42) can self-assemble into small, stable globular assemblies free of fibrils and protofibrils. Absence of large molecules was verified by atomic force microscopy (AFM) and nondenaturing gel electrophoresis. Denaturing electrophoresis revealed that the globular assemblies comprised oligomers ranging from trimers to 24mers. Oligomers prepared at 4 degrees C stayed fibril-free for days and remained so when shifted to 37 degrees C, although the spectrum of sizes shifted toward larger oligomers at the higher temperature. The soluble, globular Abeta(1-42) oligomers were toxic to PC12 cells, impairing reduction of MTT and interfering with ERK and Rac signal transduction. Occasionally, oligomers were neither toxic nor recognized by toxicity-neutralizing antibodies, suggesting that oligomers could assume alternative conformations. Tests for oligomerization-blocking activity were carried out by dot-blot immunoassays and showed that neuroprotective extracts of Ginkgo biloba could inhibit oligomer formation at very low doses. The observed neurotoxicity, structure, and stability of synthetic Abeta(1-42) globular assemblies support the hypothesis that Abeta(1-42) oligomers play a role in triggering nerve cell dysfunction and death in Alzheimer's disease.

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  51. Abbreviations Aβ, amyloid beta peptide

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Metadata

Authors
Chromy, B. A., Nowak, R. J., Lambert, M. P., Viola, K. L., Chang, L., Velasco, P. T., Jones, B. W., Fernandez, S. J., Lacor, P. N., Horowitz, P., Finch, C. E., Krafft, G. A., & Klein, W. L.
Affiliations
Northwestern University (US)
Corresponding author
Klein, William L.
ORCID
Venue
Biochemistry
Publisher
American Chemical Society (ACS)
Published
2003-10-17
Volume
42
Issue
44
Pages
12749-12760
ISSN
  • 0006-2960 (ISSN-L)
  • 1520-4995
DOI
10.1021/bi030029q
OpenAlex
W1964741226
Cited by
522
References
28
Citations by year
2026: 10 · 2025: 11 · 2024: 10 · 2023: 11 · 2022: 18 · 2021: 11 · 2020: 12 · 2019: 8 · 2018: 17 · 2017: 19 · 2016: 10 · 2015: 26 · 2014: 26 · 2013: 33 · 2012: 37
FWCI
15.33
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (1p01ag015501-01)
  • National Institute on Aging (P01-AG15501, R01-AG18877, R01AG018877)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords
amyloid-beta 42, peptide self-assembly, oligomerization, Alzheimer's disease, ERK signaling, Rac signaling, oligomer conformation
MeSH terms
Animals, Epitopes, Body Temperature, Cell Survival, Diffusion, Humans, Ligands, Neurotoxins, Nitroblue Tetrazolium, Peptide Fragments, Plant Extracts, Protein Conformation, Amyloid beta-Peptides, PC12 Cells, Neuroprotective Agents, Ginkgo biloba, Rats

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