Evidence map›Paper›PMID 24024140›Full record

ArticleRedox biology2013

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

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Redox biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
7.9field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

60 citing papers in PubMed, 119 citations in OpenAlex.

  1. Skin Histology ofAntioxidants (Basel, Switzerland) · 2026
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  7. Article
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  10. Alzheimer's disease in elderly COVID-19 patients: potential mechanisms and preventive measures.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021
    Review
  11. Article
  12. Review
  13. Review
  14. Positive association of a Sirt1 variant and parameters of oxidative stress on Alzheimer's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021
    Article
  15. Article
  16. Article
  17. Review
  18. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Sarita S HardasDepartment of Chemistry, University of Kentucky, Lexington, KY 40506-0055, USA ; Center for Membrane Sciences, University of Kentucky, Lexington, KY 40506-0055, USA ; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506-0055, USA.
Rukhsana Sultana
Amy M Clark
Tina L Beckett
Luke I Szweda
M Paul Murphy
D Allan Butterfield
University of Kentucky · USCase Western Reserve University · US

Funding

TROPIC, CHOLINERGIC AND PATHOLOGIC CHANGES IN ALZHEIMER'S DISEASEP01AG005119 · NIA · UNIVERSITY OF KENTUCKY · PI ST CLAIR, DARET K · 1985 to 2012
$15.4M
NIA NIH HHS AG-05119NIA NIH HHS P01 AG005119
6 · The paper itself

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 neurofibrillary 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. To investigate this phenomenon further, the levels and activity of lipoamide dehydrogenase (LADH) were measured in AD and control brains. Additionally, LADH activities were measured after 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 oxidative dysfunction 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.

Indexed as

AldehydesAlzheimer DiseaseAnimalsBrainCase-Control StudiesDihydrolipoamide DehydrogenaseHumansMaleMiceMice, Inbred C57BLOxidative StressThioctic Acid4-hydroxy-2-nonenalAldehydesDihydrolipoamide DehydrogenaseThioctic Acid4-hydroxy-2-trans nonenal (HNE)AD, Alzheimer diseaseAlzheimer diseaseHNE, 4-hydroxy-2-trans nonenalHNE-LA, HNE-bound lipoic acidIPL, inferior parietal lobuleLADH, lipoamide dehydrogenase/dihydrolipoamide dehydrogenaseLA, lipoic acidLipid peroxidationLipoamide dehydrogenaseLipoic acid

Identifiers

PMID24024140
PMCPMC3757677
OpenAlexW2039562082

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.