Oxidative modification of lipoic acid by HNE in alzheimer disease brain

Sarita S. Hardas, Rukhsana Sultana, Amy M. Clark, Tina L. Beckett, Luke I. Szweda, M. Paul Murphy, D. Allan Butterfield

Research output: Contribution to journalArticle

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Abstract

Alzheimer disease (AD) is an age-related neurodegenerative disease characterized by the presence of three pathological hallmarks: synapse loss, extracellular senile plaques (SP) and intracellular neurofi-brillary tangles (NFTs). The major component of SP is amyloid β-peptide (Aβ), which has been shown to induce oxidative stress. The AD brain shows increased levels of lipid peroxidation products, including 4-hydroxy-2-nonenal (HNE). HNE can react covalently with Cys, His, or Lys residues on proteins, altering structure and function of the latter. In the present study we measured the levels of the HNE-modified lipoic acid in brain of subjects with AD and age-matched controls. Lipoic acid is a key co-factor for a number of proteins including pyruvate dehydrogenase and α-ketoglutarate dehydrogenase, key complexes for cellular energetics. We observed a significant decrease in the levels of HNE-lipoic acid in the AD brain compared to that of age-matched controls. Toinvestigate this phenomenon further, the levels and activity of lipoamide dehydrogenase (LADH) were measured in AD and control brains. Additionally, LADH activities were measuredafter in-vitro HNE-treatment to mice brains. Both LADH levels and activities were found to be significantly reduced in AD brain compared to age-matched control. HNE-treatment also reduced the LADH activity in mice brain. These data are consistent with a two-hit hypothesis of AD: oxidative stress leads to lipid peroxidation that, in turn, causes oxidativedysfunction of key energy-related complexes in mitochondria, triggering neurodegeneration. This study is consonant with the notion that lipoic acid supplementation could be a potential treatment for the observed loss of cellular energetics in AD and potentiate the antioxidant defense system to prevent or delay the oxidative stress in and progression of this devastating dementing disorder.

Original languageEnglish (US)
Pages (from-to)80-85
Number of pages6
JournalRedox Biology
Volume1
Issue number1
DOIs
StatePublished - Jan 1 2013

Fingerprint

Thioctic Acid
Brain
Alzheimer Disease
Dihydrolipoamide Dehydrogenase
Oxidative stress
Oxidative Stress
Amyloid Plaques
Lipid Peroxidation
Oxidoreductases
Ketoglutarate Dehydrogenase Complex
Neurodegenerative diseases
Lipids
Mitochondria
4-hydroxy-2-nonenal
Pyruvic Acid
Amyloid
Neurodegenerative Diseases
Synapses
Proteins
Antioxidants

Keywords

  • 4-hydroxy-2-trans nonenal (HNE)
  • Alzheimer disease
  • Lipid peroxidation
  • Lipoamide dehydrogenase
  • Lipoic acid

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry

Cite this

Hardas, S. S., Sultana, R., Clark, A. M., Beckett, T. L., Szweda, L. I., Paul Murphy, M., & Butterfield, D. A. (2013). Oxidative modification of lipoic acid by HNE in alzheimer disease brain. Redox Biology, 1(1), 80-85. https://doi.org/10.1016/j.redox.2013.01.002

Oxidative modification of lipoic acid by HNE in alzheimer disease brain. / Hardas, Sarita S.; Sultana, Rukhsana; Clark, Amy M.; Beckett, Tina L.; Szweda, Luke I.; Paul Murphy, M.; Butterfield, D. Allan.

In: Redox Biology, Vol. 1, No. 1, 01.01.2013, p. 80-85.

Research output: Contribution to journalArticle

Hardas, SS, Sultana, R, Clark, AM, Beckett, TL, Szweda, LI, Paul Murphy, M & Butterfield, DA 2013, 'Oxidative modification of lipoic acid by HNE in alzheimer disease brain', Redox Biology, vol. 1, no. 1, pp. 80-85. https://doi.org/10.1016/j.redox.2013.01.002
Hardas SS, Sultana R, Clark AM, Beckett TL, Szweda LI, Paul Murphy M et al. Oxidative modification of lipoic acid by HNE in alzheimer disease brain. Redox Biology. 2013 Jan 1;1(1):80-85. https://doi.org/10.1016/j.redox.2013.01.002
Hardas, Sarita S. ; Sultana, Rukhsana ; Clark, Amy M. ; Beckett, Tina L. ; Szweda, Luke I. ; Paul Murphy, M. ; Butterfield, D. Allan. / Oxidative modification of lipoic acid by HNE in alzheimer disease brain. In: Redox Biology. 2013 ; Vol. 1, No. 1. pp. 80-85.
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