The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
Pulsed hydrogen–deuterium exchange mass spectrometry probes conformational changes in amyloid beta (Aβ) peptide aggregation
Open accessAbstract
Probing the conformational changes of amyloid beta (Aβ) peptide aggregation is challenging owing to the vast heterogeneity of the resulting soluble aggregates. To investigate the formation of these aggregates in solution, we designed an MS-based biophysical approach and applied it to the formation of soluble aggregates of the Aβ42 peptide, the proposed causative agent in Alzheimer's disease. The approach incorporates pulsed hydrogen-deuterium exchange coupled with MS analysis. The combined approach provides evidence for a self-catalyzed aggregation with a lag phase, as observed previously by fluorescence methods. Unlike those approaches, pulsed hydrogen-deuterium exchange does not require modified Aβ42 (e.g., labeling with a fluorophore). Furthermore, the approach reveals that the center region of Aβ42 is first to aggregate, followed by the C and N termini. We also found that the lag phase in the aggregation of soluble species is affected by temperature and Cu(2+) ions. This MS approach has sufficient structural resolution to allow interrogation of Aβ aggregation in physiologically relevant environments. This platform should be generally useful for investigating the aggregation of other amyloid-forming proteins and neurotoxic soluble peptide aggregates.
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“We have also recently reported that Cu2+ ions slow down fibrillization of the Aβ42 peptide and stabilize the soluble Aβ42 species, as observed by native gel electrophoresis/Western blotting, TEM, cell viability studies,20,21 and pulsed hydrogen/deuterium exchange mass spectrometry studies.22”
From Small Bifunctional Chelators That Do Not Disaggregate Amyloid β Fibrils Exhibit Reduced Cellular Toxicity (2014) · cites this paper as [22]
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“Even in the presence of Cu2+, which has been shown to stabilize the soluble Aβ42 oligomers,22 L1 and L2 were able to eliminate the neurotoxicity of soluble Aβ42 oligomers (Figure 9, lanes 9 and 10).”
From Small Bifunctional Chelators That Do Not Disaggregate Amyloid β Fibrils Exhibit Reduced Cellular Toxicity (2014) · cites this paper as [22]
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Bouakil, M. (2020) · theses.fr (ABES) · doi:10.70675/acd6af1dz6ff0z4966z9e5dzb1021e13dae0
Gupta, S., Russell, B., Kristensen, L. G., Chant, J. D., Lu, A., Obst-Huebl, L., Rad, B., Tyler, J., Subramanian, S., Kidd, S., et al. (2026) · Journal of Synchrotron Radiation · doi:10.1107/s1600577526003711
Metadata
- Authors
- Zhang, Y., Rempel, D. L., Zhang, J., Sharma, A. K., Mirica, L. M., & Gross, M. L.
- Affiliations
- California Institute of Technology (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-08-19
- Volume
- 110
- Issue
- 36
- Pages
- 14604-14609
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3767558
- OpenAlex
- W2165610594
- Cited by
- 118
- References
- 71
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 4 · 2023: 12 · 2022: 10 · 2021: 7 · 2020: 14 · 2019: 9 · 2018: 12 · 2017: 7 · 2016: 8 · 2015: 12 · 2014: 13 · 2013: 4
- FWCI
- 8.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Association (AG05681, NIRP-12-259199, 12-259199)
- Oak Ridge Associated Universities
- National Institutes of Health (GM103422, AG05681)
- Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St. Louis (P50 AG0568 1)
- National Institute on Aging (P 50 AG05681, P50AG005681)
- National Institute of General Medical Sciences (GM103422, P41GM103422)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- amyloid-beta, amyloid-beta 42, peptide aggregation, hydrogen-deuterium exchange, conformational change, lag phase, Alzheimer's disease, copper ions, temperature effects
- MeSH terms
- Alzheimer Disease, Amyloid, Copper, Deuterium, Humans, Hydrogen, Peptide Fragments, Protein Conformation, Mass Spectrometry, Temperature, Blotting, Western, Amyloid beta-Peptides, Deuterium Exchange Measurement, Microscopy, Electron, Transmission
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