Evidence map›Paper›PMID 26076991›Full record

ArticleScientific reports2015

Regulation of gamma-secretase activating protein by the 5Lipoxygenase: in vitro and in vivo evidence.

Jin Chu, Jian-Guo Li, Nicholas E Hoffman, Alexandra M Stough, Muniswamy Madesh, Domenico Praticò

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

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.9field-weighted citation impact, top 23% 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

7 citing papers in PubMed, 11 citations in OpenAlex.

  1. Gamma secretase activating protein promotes end-organ dysfunction after bacterial pneumonia.American journal of physiology. Lung cellular and molecular physiology · 2023
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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

6 authors at 1 institution in 1 country.

Jin ChuDepartment of Pharmacology, Center for Translational Medicine Temple University School of Medicine, Philadelphia, PA, USA.
Jian-Guo LiDepartment of Pharmacology, Center for Translational Medicine Temple University School of Medicine, Philadelphia, PA, USA.
Nicholas E HoffmanDepartment of Biochemistry, Center for Translational Medicine Temple University School of Medicine, Philadelphia, PA, USA.
Alexandra M StoughDepartment of Biochemistry, Center for Translational Medicine Temple University School of Medicine, Philadelphia, PA, USA.
Muniswamy MadeshDepartment of Biochemistry, Center for Translational Medicine Temple University School of Medicine, Philadelphia, PA, USA.
Domenico PraticòDepartment of Pharmacology, Center for Translational Medicine Temple University School of Medicine, Philadelphia, PA, USA.
Temple University · US

Funding

Project 3 Dysregulation of metabolic communication of oligodendrocytes and neurons by cocaine and TatP01DA037830 · NIDA · TEMPLE UNIV OF THE COMMONWEALTH · PI KHALILI, KAMEL · 2015 to 2019
$7.4M
Coordination of Pathophysiologic Endothelial Cell Signaling by ROSR01HL086699 · NHLBI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI MUNISWAMY, MADESH · 2008 to 2018
$4.3M
Inhibition of MCUR1-MCU mediated mitochondrial Ca2+ uptake prevents I/R injuryR01HL119306 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI MUNISWAMY, MADESH · 2014 to 2017
$1.6M
The Neurobiology of 5-LipoxygenaseR01AG033568 · NIA · TEMPLE UNIV OF THE COMMONWEALTH · PI PRATICO, DOMENICO · 2010 to 2014
$1.5M
PHOSPHOPROTEIN COMPONENTS OF PERICENTRIOLAR MATERIALF32GM010982 · NIGMS · UNIVERSITY OF WISCONSIN MADISON · PI FROHLICH, VICTORIA CENTONZE · 1985 to 1988
–
NHLBI NIH HHS HL086699NHLBI NIH HHS HL119306NHLBI NIH HHS R01 HL086699NHLBI NIH HHS R01 HL119306NIA NIH HHS AG33568NIA NIH HHS R01 AG033568NIDA NIH HHS P01 DA037830NIGMS NIH HHS GM10982
6 · The paper itself

Abstract

The formation of Aβ is directly controlled by the γ-secretase complex and its activator, γ-secretase activating protein (GSAP). GSAP derives from a C-terminal fragment of a larger precursor protein via a caspase-3 mediated cleavage. However, the mechanism regulating this process remains unknown. Here we provide in vitro experimental evidence that 5-Lipoxygenase (5LO) is as an endogenous regulator for GSAP formation, but not for other known γ-secretase modulators, by directly and specifically activating caspase-3. These results were confirmed in vivo by using transgenic mouse models of Alzheimer's disease in which 5LO level and activity were modulated genetically or pharmacologically. Taken together, our findings demonstrate that GSAP cleavage via caspase-3 is regulated and depend upon the availability of 5LO further establishing this protein as an attractive and viable therapeutic target for Alzheimer's disease.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesAnimalsArachidonate 5-LipoxygenaseCaspase 3Cell LineDisease Models, AnimalGene Expression RegulationHumansLipoxygenase InhibitorsMiceMice, TransgenicNeuronsProteinsProteolysisAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesArachidonate 5-LipoxygenaseCasp3 protein, mouseCaspase 3gamma-secretase activating protein, mouseLipoxygenase InhibitorsProteinsRecombinant Proteins

Identifiers

PMID26076991
PMCPMC4468577
OpenAlexW2258931252

What OpenQuestion holds

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LicenceCC BY
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.