ArticleAnnals of neurology2012
Transcriptional regulation of β-secretase-1 by 12/15-lipoxygenase results in enhanced amyloidogenesis and cognitive impairments.
Article in Annals of neurology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 21 papers.
What it found
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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.
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.
Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Metabolic alteration in oxylipins and endocannabinoids point to an important role for soluble epoxide hydrolase and inflammation in Alzheimer's disease-finding from Alzheimer's Disease Neuroimaging Initiative.Alzheimer's research & therapy · 2026Article
- Neurochemical Research of LOXBlock-1 and ZnSOBiological trace element research · 2024Article
- Downregulation of autophagy by 12/15Lipoxygenase worsens the phenotype of an Alzheimer's disease mouse model with plaques, tangles, and memory impairments.Molecular psychiatry · 2021Article
- Fair-Weather Friends: Evidence of Lipoxin Dysregulation in Neurodegeneration.Molecular nutrition & food research · 2020Review
- The effects of omega-3 fatty acid deficiency during development on oxidative fatty acid degradation during maturity in a mouse model of Alzheimer's disease.Neurobiology of aging · 2019Article
- Analysis of eicosanoid oxidation products in Alzheimer brain by LC-MS with uniformly 13C-labeled internal standards.Free radical biology & medicine · 2018Article
- Review
- Five lipoxygenase hypomethylation mediates the homocysteine effect on Alzheimer's phenotype.Scientific reports · 2017Article
- Article
- Mice deficient in L-12/15 lipoxygenase show increased vulnerability to 3-nitropropionic acid neurotoxicity.Neuroscience letters · 2017Article
- Early Growth Response 1 (Egr-1) Is a Transcriptional Activator of β-Secretase 1 (BACE-1) in the Brain.The Journal of biological chemistry · 2016Article
- The Lipoxygenases: Their Regulation and Implication in Alzheimer's Disease.Neurochemical research · 2016Article
- Pharmacologic blockade of 12/15-lipoxygenase ameliorates memory deficits, Aβ and tau neuropathology in the triple-transgenic mice.Molecular psychiatry · 2015Article
- Expression of β-site APP-cleaving enzyme 1 in the hippocampal tissue of an insulin-resistant rat model of Alzheimer's disease.Experimental and therapeutic medicine · 2015Article
- The 12/15-lipoxygenase as an emerging therapeutic target for Alzheimer's disease.Trends in pharmacological sciences · 2015Review
- Insufficient resolution response in the hippocampus of a senescence-accelerated mouse model--SAMP8.Journal of molecular neuroscience : MN · 2015Article
- Transcriptional regulation and its misregulation in Alzheimer's disease.Molecular brain · 2013Review
- Pathways to neurodegeneration: mechanistic insights from GWAS in Alzheimer's disease, Parkinson's disease, and related disorders.American journal of neurodegenerative disease · 2013Review
- Inhibition of 12/15-lipoxygenase by baicalein induces microglia PPARβ/δ: a potential therapeutic role for CNS autoimmune disease.Cell death & disease · 2013Article
- Differential contribution of lipoxygenase isozymes to nigrostriatal vulnerability.Neuroscience · 2013Article
Corrections and comments
- Retraction · 2025-01-20Concerns/Issues about Data · Concerns/Issues about Image · Duplication of/in Image · Investigation by Journal/Publisher · Investigation by Third Party · Original Data and/or Images not Provided and/or not Available · Unreliable Data · Unreliable Results and/or Conclusions ·
- Retracted
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
objective12/15-Lipoxygenase (12/15-LO) is an enzyme widely distributed in the central nervous system, and it has been involved in the neurobiology of Alzheimer disease (AD). However, the mechanism involved remains elusive.
methodsWe investigated the molecular mechanism by which 12/15-LO regulates amyloid β (Aβ)/Aβ precursor protein (APP) metabolism in vivo and in vitro by genetic and pharmacologic approaches.
resultsHere we show that overexpression of 12/15-LO leads to increased levels of β-secretase-1 (BACE1) mRNA and protein, a significant elevation in Aβ levels and deposition, and a worsening of memory deficits in AD transgenic mice. In vitro and in vivo studies demonstrate that 12/15-LO regulates BACE1 mRNA expression levels via the activation of the transcription factor Sp1. Thus, 12/15-LO-overexpressing mice had elevated levels of Sp1 and BACE1, whereas 12/15-LO-deficient mice had reduced levels of both. Preventing Sp1 activation by pharmacologic inhibition or dominant-negative mutant blocks the 12/15-LO-dependent elevation of Aβ and BACE1 levels.
interpretationOur findings demonstrate a novel pathway by which 12/15-LO increases the amyloidogenic processing of APP through a Sp1-mediated transcriptional control of BACE1 levels that could have implications for AD pathogenesis and therapy.
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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.