Evidence map›Paper›PMID 39778888›Full record

ArticleJournal of medicinal chemistry2025

Modulation of Mitochondria-Endoplasmic Reticulum Contacts (MERCs) by Small Molecules as a New Strategy for Restoring Lipid Metabolism in an Amyotrophic Lateral Sclerosis Model.

Mikel Etxebeste-Mitxeltorena, Hector Flores-Romero, Sandra Ramos-Inza, Esther Masiá, Maria Nenchova, Jorge Montesinos, Loreto Martinez-Gonzalez, Gracia Porras, Mar Orzáez, María J Vicent and 4 more

Abstract read
In one paragraph

Article in Journal of medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Review
  9. 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

14 authors.

Mikel Etxebeste-MitxeltorenaCentro de Investigaciones Biológicas "Margarita Salas"-CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain.
Hector Flores-RomeroInstitute for Genetics, CECAD, University of Cologne, Joseph-Stelzmann-Strasse 26, 50931 Cologne, Germany.
Sandra Ramos-InzaCentro de Investigaciones Biológicas "Margarita Salas"-CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain.
Esther MasiáPolymer Therapeutics Lab and Screening Platform, Príncipe Felipe Research Center (CIPF), Av. Eduardo Primo Yúfera 3, 46012 Valencia, Spain.
Maria NenchovaInstitute for Genetics, CECAD, University of Cologne, Joseph-Stelzmann-Strasse 26, 50931 Cologne, Germany.
Jorge MontesinosCentro de Investigaciones Biológicas "Margarita Salas"-CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain.
Loreto Martinez-GonzalezCentro de Investigaciones Biológicas "Margarita Salas"-CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain.
Gracia PorrasCentro de Investigaciones Biológicas "Margarita Salas"-CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain.
Mar OrzáezTargeted Therapies on Cancer and Inflammation, Príncipe Felipe Research Center (CIPF), Av. Eduardo Primo Yúfera 3, 46012 Valencia, Spain.
María J VicentPolymer Therapeutics Lab and Screening Platform, Príncipe Felipe Research Center (CIPF), Av. Eduardo Primo Yúfera 3, 46012 Valencia, Spain.ORCID 0000-0001-7771-3373
Carmen GilCentro de Investigaciones Biológicas "Margarita Salas"-CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain.ORCID 0000-0002-3882-6081
Estela Area-GomezCentro de Investigaciones Biológicas "Margarita Salas"-CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain.
Ana J Garcia-SaezInstitute for Genetics, CECAD, University of Cologne, Joseph-Stelzmann-Strasse 26, 50931 Cologne, Germany.ORCID 0000-0002-3894-5945
Ana MartinezCentro de Investigaciones Biológicas "Margarita Salas"-CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain.ORCID 0000-0002-2707-8110

Funding

European Research Council
6 · The paper itself

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease without effective treatment. The progressive motoneuron death in ALS is associated with alterations in lipid metabolism. As its regulation occurs in mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), modulation of mitochondria-ER contacts (MERCs) is emerging as a crucial factor in MAM formation and lipid metabolism control. Using the MERLIN biosensor in a high-throughput screening within the EU-OPENSCREEN ERIC, we discovered small molecules that increase MERCs in HCT116 cells, enhancing their ability to uptake cholesterol. We demonstrated that cholesterol trafficking is decreased in an ALS patient-derived cell model, and this trafficking is restored after treatment with the discovered MERC modulator

Indexed as

Amyotrophic Lateral SclerosisEndoplasmic ReticulumLipid MetabolismMitochondriaSmall Molecule LibrariesCholesterolHCT116 CellsHumansMitochondria Associated MembranesCholesterolSmall Molecule Libraries

Identifiers

PMID39778888
PMCPMC11770630

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.