Novel Antioxidants Protect Mitochondria from the Effects of Oligomeric Amyloid Beta and Contribute to the Maintenance of Epigenome Function

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10 Citations (Scopus)

Abstract

Alzheimer's disease is associated with metabolic deficits and reduced mitochondrial function, with the latter due to the effects of oligomeric amyloid beta peptide (AβO) on the respiratory chain. Recent evidence has demonstrated reduction of epigenetic markers, such as DNA methylation, in Alzheimer's disease. Here we demonstrate a link between metabolic and epigenetic deficits via reduction of mitochondrial function which alters the expression of mediators of epigenetic modifications. AβO-induced loss of mitochondrial function in differentiated neuronal cells was reversed using two novel antioxidants (1 and 2); both have been shown to mitigate the effects of reactive oxygen species (ROS), and compound 1 also restores adenosine triphosphate (ATP) levels. While both compounds were effective in reducing ROS, restoration of ATP levels was associated with a more robust response to AβO treatment. Our in vitro system recapitulates key aspects of data from Alzheimer's brain samples, the expression of epigenetic genes in which are also shown to be normalized by the novel analogues. (Figure Presented).

Original languageEnglish (US)
Pages (from-to)588-598
Number of pages11
JournalACS Chemical Neuroscience
Volume6
Issue number4
DOIs
StatePublished - Apr 15 2015

Fingerprint

Mitochondria
Amyloid
Epigenomics
Antioxidants
Maintenance
Reactive Oxygen Species
Adenosine Triphosphate
Alzheimer Disease
Oxygen Compounds
Amyloid beta-Peptides
Restoration
Brain
DNA Methylation
Electron Transport
Genes
Gene Expression

Keywords

  • Alzheimer's disease
  • epigenetics
  • Mitochondria
  • multifunctional radical quenchers

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Physiology
  • Cognitive Neuroscience

Cite this

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title = "Novel Antioxidants Protect Mitochondria from the Effects of Oligomeric Amyloid Beta and Contribute to the Maintenance of Epigenome Function",
abstract = "Alzheimer's disease is associated with metabolic deficits and reduced mitochondrial function, with the latter due to the effects of oligomeric amyloid beta peptide (AβO) on the respiratory chain. Recent evidence has demonstrated reduction of epigenetic markers, such as DNA methylation, in Alzheimer's disease. Here we demonstrate a link between metabolic and epigenetic deficits via reduction of mitochondrial function which alters the expression of mediators of epigenetic modifications. AβO-induced loss of mitochondrial function in differentiated neuronal cells was reversed using two novel antioxidants (1 and 2); both have been shown to mitigate the effects of reactive oxygen species (ROS), and compound 1 also restores adenosine triphosphate (ATP) levels. While both compounds were effective in reducing ROS, restoration of ATP levels was associated with a more robust response to AβO treatment. Our in vitro system recapitulates key aspects of data from Alzheimer's brain samples, the expression of epigenetic genes in which are also shown to be normalized by the novel analogues. (Figure Presented).",
keywords = "Alzheimer's disease, epigenetics, Mitochondria, multifunctional radical quenchers",
author = "Diego Mastroeni and Omar Khdour and Arce, {Pablo M.} and Sidney Hecht and Paul Coleman",
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T1 - Novel Antioxidants Protect Mitochondria from the Effects of Oligomeric Amyloid Beta and Contribute to the Maintenance of Epigenome Function

AU - Mastroeni, Diego

AU - Khdour, Omar

AU - Arce, Pablo M.

AU - Hecht, Sidney

AU - Coleman, Paul

PY - 2015/4/15

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N2 - Alzheimer's disease is associated with metabolic deficits and reduced mitochondrial function, with the latter due to the effects of oligomeric amyloid beta peptide (AβO) on the respiratory chain. Recent evidence has demonstrated reduction of epigenetic markers, such as DNA methylation, in Alzheimer's disease. Here we demonstrate a link between metabolic and epigenetic deficits via reduction of mitochondrial function which alters the expression of mediators of epigenetic modifications. AβO-induced loss of mitochondrial function in differentiated neuronal cells was reversed using two novel antioxidants (1 and 2); both have been shown to mitigate the effects of reactive oxygen species (ROS), and compound 1 also restores adenosine triphosphate (ATP) levels. While both compounds were effective in reducing ROS, restoration of ATP levels was associated with a more robust response to AβO treatment. Our in vitro system recapitulates key aspects of data from Alzheimer's brain samples, the expression of epigenetic genes in which are also shown to be normalized by the novel analogues. (Figure Presented).

AB - Alzheimer's disease is associated with metabolic deficits and reduced mitochondrial function, with the latter due to the effects of oligomeric amyloid beta peptide (AβO) on the respiratory chain. Recent evidence has demonstrated reduction of epigenetic markers, such as DNA methylation, in Alzheimer's disease. Here we demonstrate a link between metabolic and epigenetic deficits via reduction of mitochondrial function which alters the expression of mediators of epigenetic modifications. AβO-induced loss of mitochondrial function in differentiated neuronal cells was reversed using two novel antioxidants (1 and 2); both have been shown to mitigate the effects of reactive oxygen species (ROS), and compound 1 also restores adenosine triphosphate (ATP) levels. While both compounds were effective in reducing ROS, restoration of ATP levels was associated with a more robust response to AβO treatment. Our in vitro system recapitulates key aspects of data from Alzheimer's brain samples, the expression of epigenetic genes in which are also shown to be normalized by the novel analogues. (Figure Presented).

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KW - epigenetics

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