Evidence map›Paper›PMID 28134307›Full record

ArticleScientific reports2017

Fingolimod Limits Acute Aβ Neurotoxicity and Promotes Synaptic Versus Extrasynaptic NMDA Receptor Functionality in Hippocampal Neurons.

Pooja Joshi, Martina Gabrielli, Luisa Ponzoni, Silvia Pelucchi, Matteo Stravalaci, Marten Beeg, Sonia Mazzitelli, Daniela Braida, Mariaelvina Sala, Enrica Boda and 6 more

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 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

22 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
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  7. Novel therapeutic approaches to target neurodegeneration.British journal of pharmacology · 2023
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  18. Animal Models of Psychosis in Alzheimer Disease.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2020
    Review
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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

16 authors at 5 institutions in 1 country.

Pooja JoshiIRCCS Humanitas, via Manzoni 56, 20089 Rozzano, Italy.
Martina GabrielliCNR Institute of Neuroscience, via Vanvitelli 32, 20129 Milano, Italy.
Luisa PonzoniDepartment of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, via Vanvitelli 32, 20129 Milano, Italy.
Silvia PelucchiDepartment of Pharmacological and Biomolecular Sciences, University of Milan, via Balzaretti 9, 20133 Milan, Italy.
Matteo StravalaciDepartment of Molecular Biochemistry and Pharmacology IRCSS - Istituto di Ricerche Farmacologiche Mario Negri, via La Masa 19, 20156 Milan, Italy.
Marten BeegDepartment of Molecular Biochemistry and Pharmacology IRCSS - Istituto di Ricerche Farmacologiche Mario Negri, via La Masa 19, 20156 Milan, Italy.
Sonia MazzitelliIRCCS Humanitas, via Manzoni 56, 20089 Rozzano, Italy.
Daniela BraidaDepartment of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, via Vanvitelli 32, 20129 Milano, Italy.
Mariaelvina SalaCNR Institute of Neuroscience, via Vanvitelli 32, 20129 Milano, Italy.
Enrica BodaDepartment of Neuroscience Rita Levi-Montalcini, University of Turin, 10126, Turin, Italy.
Annalisa BuffoDepartment of Neuroscience Rita Levi-Montalcini, University of Turin, 10126, Turin, Italy.
Marco GobbiDepartment of Molecular Biochemistry and Pharmacology IRCSS - Istituto di Ricerche Farmacologiche Mario Negri, via La Masa 19, 20156 Milan, Italy.
Fabrizio GardoniDepartment of Pharmacological and Biomolecular Sciences, University of Milan, via Balzaretti 9, 20133 Milan, Italy.
Michela MatteoliIRCCS Humanitas, via Manzoni 56, 20089 Rozzano, Italy.
Elena MarcelloDepartment of Pharmacological and Biomolecular Sciences, University of Milan, via Balzaretti 9, 20133 Milan, Italy.
Claudia VerderioIRCCS Humanitas, via Manzoni 56, 20089 Rozzano, Italy.
University of Milan · ITIRCCS Humanitas Research Hospital · ITMario Negri Institute for Pharmacological Research · ITNeuroscience Institute · ITUniversity of Turin · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Fingolimod, also known as FTY720, is an analogue of the sphingolipid sphingosine, which has been proved to be neuroprotective in rodent models of Alzheimer's disease (AD). Several cellular and molecular targets underlying the neuroprotective effects of FTY720 have been recently identified. However, whether the drug directly protects neurons from toxicity of amyloid-beta (Aβ) still remains poorly defined. Using a combination of biochemical assays, live imaging and electrophysiology we demonstrate that FTY720 induces a rapid increase in GLUN2A-containing neuroprotective NMDARs on the surface of dendritic spines in cultured hippocampal neurons. In addition, the drug mobilizes extrasynaptic GLUN2B-containing NMDARs, which are coupled to cell death, to the synapses. Altered ratio of synaptic/extrasynaptic NMDARs decreases calcium responsiveness of neurons to neurotoxic soluble Aβ 1-42 and renders neurons resistant to early alteration of calcium homeostasis. The fast defensive response of FTY720 occurs through a Sphingosine-1-phosphate receptor (S1P-R) -dependent mechanism, as it is lost in the presence of S1P-R1 and S1P-R3 antagonists. We propose that rapid synaptic relocation of NMDARs might have direct impact on amelioration of cognitive performance in transgenic APPswe/PS1dE9 AD mice upon sub-chronic treatment with FTY720.

Indexed as

AmyloidAmyloid beta-PeptidesAnimalsCalciumCell MembraneFingolimod HydrochlorideMemoryMiceMice, TransgenicNeuroprotective AgentsProtein AggregatesProtein Aggregation, PathologicalProtein BindingPyramidal CellsReceptors, N-Methyl-D-AspartateSynapsesAmyloidAmyloid beta-PeptidesCalciumFingolimod HydrochlorideNeuroprotective AgentsNR2B NMDA receptorProtein AggregatesReceptors, N-Methyl-D-Aspartate

Identifiers

PMID28134307
PMCPMC5278353
OpenAlexW2581871327

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.