Redox proteomics and amyloid β-peptide: insights into Alzheimer disease

D. Allan Butterfield, Debra Boyd-Kimball

Research output: Contribution to journalReview articlepeer-review

81 Scopus citations

Abstract

Alzheimer disease (AD) is a progressive neurodegenerative disorder associated with aging and characterized pathologically by the presence of senile plaques, neurofibrillary tangles, and neurite and synapse loss. Amyloid beta-peptide (1–42) [Aβ(1–42)], a major component of senile plaques, is neurotoxic and induces oxidative stress in vitro and in vivo. Redox proteomics has been used to identify proteins oxidatively modified by Aβ(1–42) in vitro and in vivo. In this review, we discuss these proteins in the context of those identified to be oxidatively modified in animal models of AD, and human studies including familial AD, pre-clinical AD (PCAD), mild cognitive impairment (MCI), early AD, late AD, Down syndrome (DS), and DS with AD (DS/AD). These redox proteomics studies indicate that Aβ(1–42)-mediated oxidative stress occurs early in AD pathogenesis and results in altered antioxidant and cellular detoxification defenses, decreased energy yielding metabolism and mitochondrial dysfunction, excitotoxicity, loss of synaptic plasticity and cell structure, neuroinflammation, impaired protein folding and degradation, and altered signal transduction. Improved access to biomarker imaging and the identification of lifestyle interventions or treatments to reduce Aβ production could be beneficial in preventing or delaying the progression of AD. (Figure presented.) This article is part of the special issue "Proteomics".

Original languageEnglish
Pages (from-to)459-487
Number of pages29
JournalJournal of Neurochemistry
Volume151
Issue number4
DOIs
StatePublished - Nov 1 2019

Bibliographical note

Publisher Copyright:
© 2018 International Society for Neurochemistry

Keywords

  • Alzheimer disease
  • amyloid β-peptide
  • oxidative stress
  • redox proteomics

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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