Evidence map›Paper›PMID 24808180›Full record

ArticleThe Journal of biological chemistry2014

Deficiency of sphingosine-1-phosphate lyase impairs lysosomal metabolism of the amyloid precursor protein.

Ilker Karaca, Irfan Y Tamboli, Konstantin Glebov, Josefine Richter, Lisa H Fell, Marcus O Grimm, Viola J Haupenthal, Tobias Hartmann, Markus H Gräler, Gerhild van Echten-Deckert and 1 more

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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 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
2.8field-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

41 citing papers in PubMed, 58 citations in OpenAlex.

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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

11 authors at 4 institutions in 1 country.

Ilker KaracaFrom the Department of Neurology, University of Bonn, 53127 Bonn, Germany.
Irfan Y TamboliFrom the Department of Neurology, University of Bonn, 53127 Bonn, Germany.
Konstantin GlebovFrom the Department of Neurology, University of Bonn, 53127 Bonn, Germany.
Josefine RichterGerman Center for Neurodegenerative Diseases (DZNE), 53175 Bonn, Germany.
Lisa H Fellthe Department of Experimental Neurology, University of the Saarland, 66421 Homburg/Saar, Germany.
Marcus O Grimmthe Department of Experimental Neurology, University of the Saarland, 66421 Homburg/Saar, Germany.
Viola J Haupenthalthe Department of Experimental Neurology, University of the Saarland, 66421 Homburg/Saar, Germany.
Tobias Hartmannthe Department of Experimental Neurology, University of the Saarland, 66421 Homburg/Saar, Germany.
Markus H Grälerthe Department of Anaesthesiology and Intensive Care Medicine, Center for Sepsis Control and Care, and Center for Molecular Biomedicine, University Hospital Jena, 07740 Jena, Germany, and.
Gerhild van Echten-Deckertthe Life and Medical Sciences, Membrane Biology and Lipid Biochemistry Unit at the Kekulé-Institute, University of Bonn, 53121 Bonn, Germany.
Jochen WalterFrom the Department of Neurology, University of Bonn, 53127 Bonn, Germany, Jochen.Walter@ukb.uni-bonn.de.
University of Bonn · DESaarland University · DEGerman Center for Neurodegenerative Diseases · DEJena University Hospital · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Progressive accumulation of the amyloid β protein in extracellular plaques is a neuropathological hallmark of Alzheimer disease. Amyloid β is generated during sequential cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. In addition to the proteolytic processing by secretases, APP is also metabolized by lysosomal proteases. Here, we show that accumulation of intracellular sphingosine-1-phosphate (S1P) impairs the metabolism of APP. Cells lacking functional S1P-lyase, which degrades intracellular S1P, strongly accumulate full-length APP and its potentially amyloidogenic C-terminal fragments (CTFs) as compared with cells expressing the functional enzyme. By cell biological and biochemical methods, we demonstrate that intracellular inhibition of S1P-lyase impairs the degradation of APP and CTFs in lysosomal compartments and also decreases the activity of γ-secretase. Interestingly, the strong accumulation of APP and CTFs in S1P-lyase-deficient cells was reversed by selective mobilization of Ca(2+) from the endoplasmic reticulum or lysosomes. Intracellular accumulation of S1P also impairs maturation of cathepsin D and degradation of Lamp-2, indicating a general impairment of lysosomal activity. Together, these data demonstrate that S1P-lyase plays a critical role in the regulation of lysosomal activity and the metabolism of APP.

Indexed as

Aldehyde-LyasesAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAnimalsCalciumCathepsin DHEK293 CellsHumansLysophospholipidsLysosomal-Associated Membrane Protein 2LysosomesMiceProteolysisSphingosineAldehyde-LyasesAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesCalciumCathepsin DLysophospholipidsLysosomal-Associated Membrane Protein 2Sphingosinesphingosine 1-phosphatesphingosine 1-phosphate lyase (aldolase)Alzheimer DiseaseAmyloidAmyloid Precursor Protein (APP)LysosomeSphingolipidSphingosine-1-phosphate (S1P)

Identifiers

PMID24808180
PMCPMC4059120
OpenAlexW2016002923

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.