Cited by 125Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchParkinson's Disease Mechanisms and Treatments

Methionine-35 of A β (1–42): Importance for Oxidative Stress in Alzheimer Disease

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Butterfield, D. Allan, Sultana, Rukhsana·2011·Journal of Amino Acids

Abstract

Alzheimer disease (AD) is an age-related progressive neurodegenerative disorder. This devastating disease is characterized by the presence of senile plaques (SP), neurofibrillary tangles (NFTs), and loss of synapses. Amyloid beta-peptide 1–42 (A β (1–42)) is the main component of SP and is pivotal to AD pathogenesis. Brain of subjects with AD and arguably its earliest manifestation, mild cognitive impairment (MCI), demonstrate increased levels of oxidative stress markers. Our laboratory combined these two aspects of AD and MCI and proposed the A β (1–42)-associated free radical oxidative stress hypothesis to explain oxidative stress under which the MCI and AD brain exist and the loss of synapses in both disorders. A large number of in vitro and in vivo studies showed that A β causes protein oxidation, lipid peroxidation, reactive oxygen species formation, and cell death in neuronal and synaptosomal systems. Methionine located at residue 35 of A β (1–42) is an important contributor to the oxidative stress associated with this neurotoxic peptide. In this paper, we summarize studies involving Met-35 of A β (1–42). Understanding the role of the single methionine residue of A β (1–42) may help in understanding underlying disease mechanisms in AD and MCI.

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  • AI-based analytical methods are increasingly used for enrichment, site identification, and functional network modeling of PTMs.

    “Given the complexity and low abundance of many PTMs, AI-based analytical methods are increasingly used for enrichment, site identification, and functional network modeling139,169,178,179.”

    From Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions (2025) · cites this paper as [139]

    Section 7 describes redox proteomics used to identify oxidatively modified proteins and altered brain pathways, but it does not describe AI-based methods. Searches for AI, enrichment, PTM site identification, and functional network modeling found no passage addressing those uses; the cited paper’s focus is methionine-35 and oxidative stress. (LLM, conf=0.76)

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Research works printed but not linked: 5

  1. [2]Bertram L Alzheimer’s disease genetics current status and future perspectives International Review of Neurobiology 2009 84 167 184 19501718
  2. [14]Yatin SM Varadarajan S Link CD Butterfield DA In vitro and in vivo oxidative stress associated with Alzheimer’s amyloid beta-peptide (1–42) Neurobiology of Aging 1999 20 3 325 330 10588580
  3. [21]Yao Y Zhukareva V Sung S Enhanced brain levels of 8,12-iso-iPF2alpha-VI differentiate AD from frontotemporal dementia Neurology 2003 61 4 475 478 12939420
  4. [61]Murray MM Bernstein SL Nyugen VY Condron MM Teplow DB Bowers MT Amyloid beta protein: a beta40 Inhibits A β42 oligomerization Journal of the American Chemical Society 2009 131 18 6316 6317 19385598 PMC2697393
  5. [84]Ritchie CW Bush AI Mackinnon A Metal-protein attenuation with iodochlorhydroxyquin (Clioquinol) targeting Aβ amyloid deposition and toxicity in alzheimer disease Archives of Neurology 2003 60 12 1685 1691 14676042

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Authors
Butterfield, D. A., & Sultana, R.
Affiliations
  • University of Kentucky (US)
  • Department of Chemistry, University of Kentucky, Lexington, KY 40506-0055, USA
Corresponding author
Butterfield, D. Allan
Venue
Journal of Amino Acids
Publisher
Wiley
Published
2011-06-04
Volume
2011
Pages
1-10
ISSN
  • 2090-0104 (ISSN-L)
  • 2090-0112
OpenAlex
W2015089109
Cited by
124
References
95
Citations by year
2026: 2 · 2025: 6 · 2024: 11 · 2023: 26 · 2022: 5 · 2021: 6 · 2020: 7 · 2019: 6 · 2018: 8 · 2017: 8 · 2016: 6 · 2015: 6 · 2014: 8 · 2013: 9 · 2012: 9
FWCI
6.11
Type
journal article
Language
en
Open access
Locations
  • Journal of Amino Acids (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UKnowledge (University of Kentucky) (submittedVersion, cc-by)
Funders
National Institutes of Health (AG-05119)
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 › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords
Alzheimer's disease, amyloid beta peptide 1-42, 35S-methionine, oxidative stress, mild cognitive impairment, amyloid plaques, neurofibrillary tangles, synaptic loss, protein oxidation, lipid peroxidation, reactive oxygen species, neurotoxicity

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