Evidence map›Paper›PMID 24352696›Full record

ArticleThe Journal of biological chemistry2014

MicroRNA-339-5p down-regulates protein expression of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) in human primary brain cultures and is reduced in brain tissue specimens of Alzheimer disease subjects.

Justin M Long, Balmiki Ray, Debomoy K Lahiri

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

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed, 4 pooled it
6.3field-weighted citation impact, top 3% 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

115 citing papers in PubMed, 4 syntheses or guidelines pooled it, 185 citations in OpenAlex.

  1. Pooled it
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  13. Plasma miRNAs across the Alzheimer's disease continuum: Relationship to central biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  14. Role of miRNAs in neurovascular injury and repair.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024
    Review
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55 more citing papers are in PubMed but not listed here.

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

3 authors at 2 institutions in 1 country.

Justin M LongFrom the Laboratory of Molecular Neurogenetics, Institute of Psychiatric Research, Departments of Psychiatry and.
Balmiki Ray
Debomoy K Lahiri
Indiana University – Purdue University Indianapolis · USIndiana University School of Medicine

Funding

Regulation of APP Pathway Gene Promoters in Alzheimer'sR01AG018379 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI LAHIRI, DEBOMOY K · 2000 to 2011
$3.1M
Mechanisms of Cholinesterase Inhibitors on Beta-amyloidR01AG018884 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI LAHIRI, DEBOMOY K · 2002 to 2012
$2.9M
Microtubule-associated regulation of acute lung injuryR01HL107920 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI BIRUKOVA, ANNA · 2011 to 2019
$2.8M
Human MicroRNA as a potential therapeutic target in Alzheimer's disease.R21AG042804 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI LAHIRI, DEBOMOY K · 2012 to 2013
$411k
Microtubule-associated regulation of acute lung injuryR56HL107920 · NHLBI · UNIVERSITY OF CHICAGO · PI BIRUKOVA, ANNA · 2015 to 2015
$395k
NHLBI NIH HHS HL107920NIA NIH HHS AG042804NIA NIH HHS AG18884NIA NIH HHS R01 AG018379NIA NIH HHS R01 AG018884NIA NIH HHS R21 AG042804
6 · The paper itself

Abstract

Alzheimer disease (AD) results, in part, from the excess accumulation of the amyloid-β (Aβ) peptide as neuritic plaques in the brain. The short Aβ peptide is derived from the large transmembrane Aβ precursor protein (APP). The rate-limiting step in the production of Aβ from APP is mediated by the β-site APP-cleaving enzyme 1 (BACE1). Dysregulation of BACE1 levels leading to excess Aβ deposition is implicated in sporadic AD. Thus, elucidating the full complement of regulatory pathways that control BACE1 expression is key to identifying novel drug targets central to the Aβ-generating process. MicroRNAs (miRNAs) are expected to participate in this molecular network. Here, we identified a known miRNA, miR-339-5p, as a key contributor to this regulatory network. Two distinct miR-339-5p target sites were predicted in the BACE1 3'-UTR by in silico analyses. Co-transfection of miR-339-5p with a BACE1 3'-UTR reporter construct resulted in significant reduction in reporter expression. Mutation of both target sites eliminated this effect. Delivery of the miR-339-5p mimic also significantly inhibited expression of BACE1 protein in human glioblastoma cells and human primary brain cultures. Delivery of target protectors designed against the miR-339-5p BACE1 3'-UTR target sites in primary human brain cultures significantly elevated BACE1 expression. Finally, miR-339-5p levels were found to be significantly reduced in brain specimens isolated from AD patients as compared with age-matched controls. Therefore, miR-339-5p regulates BACE1 expression in human brain cells and is most likely dysregulated in at least a subset of AD patients making this miRNA a novel drug target.

Indexed as

3' Untranslated RegionsAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesArgonaute ProteinsAspartic Acid EndopeptidasesBase SequenceBrainCell Line, TumorCells, CulturedCell ShapeComputational BiologyConserved SequenceDemography3' Untranslated RegionsAGO2 protein, humanAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesArgonaute ProteinsAspartic Acid EndopeptidasesBACE1 protein, humanMicroRNAsMIRN339 microRNA, humanAgingAlzheimer DiseaseDementiaGene RegulationHuman Brain TissueHuman NeuronMicroRNANoncoding RNASecretasesβ-Peptide

Identifiers

PMID24352696
PMCPMC3931075
OpenAlexW2001712818

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.