Evidence map›Paper›PMID 40123295›Full record

ArticleThe FEBS journal2025

Natural aminosterols inhibit NMDA receptors with low nanomolar potency.

Giulia Fani, Elisabetta Coppi, Silvia Errico, Federica Cherchi, Martina Gennari, Denise Barbut, Michele Vendruscolo, Michael Zasloff, Anna Maria Pugliese, Fabrizio Chiti

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The FEBS journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
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

10 authors.

Giulia FaniDepartment of Experimental and Clinical Biomedical Sciences, Section of Biochemistry, University of Florence, Italy.
Elisabetta CoppiDepartment of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Division of Pharmacology and Toxicology, University of Florence, Italy.
Silvia ErricoDepartment of Experimental and Clinical Biomedical Sciences, Section of Biochemistry, University of Florence, Italy.
Federica CherchiDepartment of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Division of Pharmacology and Toxicology, University of Florence, Italy.
Martina GennariDepartment of Experimental and Clinical Biomedical Sciences, Section of Biochemistry, University of Florence, Italy.
Denise BarbutEnterin Research Institute Inc., Philadelphia, PA, USA.
Michele VendruscoloCentre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, UK.ORCID 0000-0002-3616-1610
Michael ZasloffEnterin Research Institute Inc., Philadelphia, PA, USA.
Anna Maria PuglieseDepartment of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Division of Pharmacology and Toxicology, University of Florence, Italy.
Fabrizio ChitiDepartment of Experimental and Clinical Biomedical Sciences, Section of Biochemistry, University of Florence, Italy.ORCID 0000-0002-1330-1289

Funding

Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di FirenzeMinistero dell'Università e della RicercaProgetto Dipartimenti di Eccellenza 2022-2027Regione Toscana
6 · The paper itself

Abstract

Abnormal functions of N-methyl-D-aspartate receptors (NMDARs) are associated with many brain disorders, making them primary targets for drug discovery. We show that natural aminosterols inhibit the NMDAR-mediated increase of intracellular calcium ions in cultured primary neurons and neuroblastoma cells. Structural comparison with known NMDAR-negative allosteric modulators, such as pregnanolone-sulfate-2 (PAS), raises the hypothesis that aminosterols have the same mechanism of action. Fluorescence resonance energy transfer (FRET) measurements using labeled NMDAR and the labeled aminosterol trodusquemine (TRO) indicate close spatial proximity, likely arising from binding. Other indirect yet plausible mechanisms for NMDAR inhibition by TRO were excluded. Electrophysiological patch clamp measurements on primary neurons indicate that pre-incubated TRO inhibits NMDA-induced ion currents with a IC

Indexed as

Receptors, N-Methyl-D-AspartateAnimalsCalciumCell Line, TumorCells, CulturedFluorescence Resonance Energy TransferHumansMiceNeuronsN-MethylaspartatePatch-Clamp TechniquesRatsCalciumN-MethylaspartateReceptors, N-Methyl-D-AspartateENT‐03ionotropic glutamate receptorsnegative allosteric modulatorsNMDA antagonistsqualamine

Identifiers

PMID40123295
PMCPMC12220853

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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.