Amyloid β Protein: Aβ40 Inhibits Aβ42 Oligomerization
Open accessAbstract
Abeta40 and Abeta42 are peptides that adopt similar random-coil structures in solution. Abeta42, however, is significantly more neurotoxic than Abeta40 and forms amyloid fibrils much more rapidly than Abeta40. Here, mass spectrometry and ion mobility spectrometry are used to investigate a mixture of Abeta40 and Abeta42. The mass spectrum for the mixed solution shows the presence of a heterooligomer composed of equal parts of Abeta40 and Abeta42. Ion mobility results indicate that this mixed species comprises an oligomer distribution extending to tetramers. Abeta40 alone produces such a distribution, whereas Abeta42 alone produces oligomers as large as dodecamers. This indicates that Abeta40 inhibits Abeta42 oligomerization.
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Almost all previous studies investigating the effect of bifunctional compounds on the neurotoxicity of metal-Aβ species have focused on the less neurotoxic and possibly even anti-amyloidogenic Aβ40 peptide.
“Almost all previous studies investigating the effect of bifunctional compounds on the neurotoxicity of metal-Aβ species have focused on the less neurotoxic and possibly even anti-amyloidogenic Aβ40 peptide.9,97,98”
From Bifunctional Compounds for Controlling Metal-Mediated Aggregation of the Aβ<sub>42</sub>Peptide (2012) · cites this paper as [97]
The paper’s Abstract (page unavailable) says Aβ42 is significantly more neurotoxic than Aβ40 and reports that Aβ40 inhibits Aβ42 oligomerization, supporting the description of Aβ40 as less neurotoxic and possibly anti-amyloidogenic. It does not address whether almost all previous studies of bifunctional compounds and metal-Aβ neurotoxicity focused on Aβ40. (LLM, conf=0.87)
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- Authors
- Murray, M. M., Bernstein, S. L., Nyugen, V., Condron, M. M., Teplow, D. B., & Bowers, M. T.
- Affiliations
- University of California, Santa Barbara (US)
- Corresponding author
- Bowers, Michael T.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2009-04-22
- Volume
- 131
- Issue
- 18
- Pages
- 6316-6317
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- PMC
- PMC2697393
- OpenAlex
- W1991634503
- Cited by
- 128
- References
- 3
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 4 · 2023: 8 · 2022: 4 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 9 · 2017: 7 · 2016: 7 · 2015: 13 · 2014: 9 · 2013: 10 · 2012: 14
- FWCI
- 8.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- U.S. Public Health Service (IPOIAG027818)
- National Institute on Aging (P01AG027818)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Keywords
- amyloid-beta, Aβ40, amyloid-beta 42, oligomerization inhibition, hetero-oligomers, amyloid fibrils, neurotoxicity, oligomer size distribution, tetramer, dodecamer, Alzheimer's disease
- MeSH terms
- Amyloid, Peptide Fragments, Spectrum Analysis, Structure-Activity Relationship, Amyloid beta-Peptides, Protein Structure, Secondary, Protein Multimerization
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