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

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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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Crossref · 10.4061/2011/198430

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Figures

Figure 1 Amyloid beta (Aβ) peptide induces oxidative stress and neuronal loss.
Figure 1 Amyloid beta (Aβ) peptide induces oxidative stress and neuronal loss.CC BY · PubMed Central
Figure 2 The sequence of amyloid beta (Aβ) peptide. Methione is present in the 35th position of Aβ(1–42).
Figure 2 The sequence of amyloid beta (Aβ) peptide. Methione is present in the 35th position of Aβ(1–42).CC BY · PubMed Central
Figure 3 Methionine-35 residues in Aβ can undergo one electron oxidation to form a sulfuranyl radical, which can then initiate the process of lipid peroxidation. For details of this proposed mechanism, please refer to the text.
Figure 3 Methionine-35 residues in Aβ can undergo one electron oxidation to form a sulfuranyl radical, which can then initiate the process of lipid peroxidation. For details of this proposed mechanism, please refer to the text.CC BY · PubMed Central

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Research works printed but not linked: 2

  1. 1991, BioFactors, 3, 91
  2. 2008, Journal of Pharmaceutical Science and Technology, 62, 211

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Metadata

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
  • 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
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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