Evidence map›Paper›PMID 28383037›Full record

ArticleScientific reports2017

Five lipoxygenase hypomethylation mediates the homocysteine effect on Alzheimer's phenotype.

Jian-Guo Li, Carlos Barrero, Salim Merali, Domenico Praticò

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.1field-weighted citation impact, top 9% 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

21 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Frontiers in neuroscience · 2025
    Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Elevated cerebrospinal fluid homocysteine is associated with blood-brain barrier disruption in amyotrophic lateral sclerosis patients.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2020
    Article
  14. Review
  15. Article
  16. Epigenetics of the Synapse in Neurodegeneration.Current neurology and neuroscience reports · 2019
    Review
  17. Article
  18. Homocysteine and Dementia: An International Consensus Statement.Journal of Alzheimer's disease : JAD · 2018
    Article
  19. Review
  20. Article
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

4 authors at 1 institution in 1 country.

Jian-Guo LiDepartment of Pharmacology and Center for Translational Medicine, Lewis Katz School of Medicine, Temple University Philadelphia, PA 19140, USA.
Carlos BarreroDepartment of Pharmaceutical Sciences, Temple University Philadelphia, PA 19140, USA.
Salim MeraliDepartment of Pharmaceutical Sciences, Temple University Philadelphia, PA 19140, USA.
Domenico PraticòDepartment of Pharmacology and Center for Translational Medicine, Lewis Katz School of Medicine, Temple University Philadelphia, PA 19140, USA.
Temple University · US

Funding

Dissecting the role of 5LO in neurodegeneration associated with homocysteineRF1AG051684 · NIA · TEMPLE UNIV OF THE COMMONWEALTH · PI PRATICO, DOMENICO · 2016 to 2016
$1.9M
5Lipoxygenase-mediated vasculopathy in HHcyR01HL112966 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI PRATICO, DOMENICO · 2013 to 2016
$1.5M
NHLBI NIH HHS R01 HL112966NIA NIH HHS RF1 AG051684
6 · The paper itself

Abstract

Environmental and genetic risk factors are implicated in the pathogenesis of Alzheimer's disease (AD). However, how they interact and influence its pathogenesis remains to be investigated. High level of homocysteine (Hcy) is an AD risk factor and associates with an up-regulation of the ALOX5 gene. In the current paper we investigated whether this activation is responsible for the Hcy effect on the AD phenotype and the mechanisms involved. Triple transgenic mice were randomized to receive regular chow diet, a diet deficient in folate and B vitamins (Diet), which results in high Hcy, or the Diet plus zileuton, a specific ALOX5 inhibitor, for 7 months. Compared with controls, Diet-fed mice had a significant increase in Hcy levels, memory and learning deficits, up-regulation of the ALOX5 pathway, increased Aβ levels, tau phosphorylation, and synaptic pathology, which were absent in mice treated with zileuton. In vivo and vitro studies demonstrated that the mechanism responsible was the hypomethylation of the ALOX5 promoter. Our findings demonstrate that the up-regulation of the ALOX5 is responsible for the Hcy-dependent worsening of the AD phenotype in a relevant mouse model of the disease. The discovery of this previously unknown cross-talk between these two pathways could afford novel therapeutic opportunities for treating or halting AD.

Indexed as

DNA MethylationAlzheimer DiseaseAmyloid beta-PeptidesAnimalsBehavior, AnimalDietFemaleFolic AcidFolic Acid DeficiencyHomocysteineHumansHydroxyureaInflammationLipoxygenaseMaleMice, TransgenicAmyloid beta-PeptidesFolic AcidHomocysteineHydroxyureaLipoxygenasetau ProteinsVitamin B Complexzileuton

Identifiers

PMID28383037
PMCPMC5382538
OpenAlexW2604485299

What OpenQuestion holds

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LicenceCC BY
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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.