Evidence map›Paper›PMID 39060641›Full record

ArticleEMBO molecular medicine2024

Dantrolene corrects cellular disease features of Darier disease and may be a novel treatment.

Matthew Hunt, Nuoqi Wang, Naricha Pupinyo, Philip Curman, Monica Torres, William Jebril, Maria Chatzinikolaou, Julie Lorent, Gilad Silberberg, Ritu Bansal and 7 more

Abstract read
In one paragraph

Article in EMBO molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. 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

17 authors.

Matthew Hunt *Dermatology and Venereology Division, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-7697-8086
Nuoqi Wang *Dermatology and Venereology Division, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden.
Naricha PupinyoDermatology and Venereology Division, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden.
Philip CurmanDermatology and Venereology Division, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden.
Monica TorresDermatology and Venereology Division, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-6634-2562
William JebrilDermatology and Venereology Division, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden.
Maria ChatzinikolaouDermatology and Venereology Division, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-3539-9088
Julie LorentNational Bioinformatics Infrastructure Sweden (NBIS), Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Gilad SilberbergBioinformatics & Computational Biology Research Operations, Champions Oncology Inc, Rehovot, Israel.
Ritu BansalDermatology and Venereology Division, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-4091-1696
Teresa BurnerJohannes Kepler University Linz, Kepler University Hospital Linz, Department of Dermatology, Linz, Austria.
Jing ZhouDepartment of Dermatology, Genetics, and Pathology, Yale University School of Medicine, New Haven, CT, USA.
Susanne KimeswengerJohannes Kepler University Linz, Kepler University Hospital Linz, Department of Dermatology, Linz, Austria.ORCID http://orcid.org/0000-0002-0443-8558
Wolfram HoetzeneckerJohannes Kepler University Linz, Kepler University Hospital Linz, Department of Dermatology, Linz, Austria.
Keith ChoateDepartment of Dermatology, Genetics, and Pathology, Yale University School of Medicine, New Haven, CT, USA.
Etty Bachar-WikstromDermatology and Venereology Division, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden. ester.bachar-wikstrom@ki.se.ORCID http://orcid.org/0000-0002-3283-6721
Jakob D WikstromDermatology and Venereology Division, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden. jakob.wikstrom@ki.se.ORCID http://orcid.org/0000-0002-9241-6817

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
NCATS NIH HHS UL1 TR001863
6 · The paper itself

Abstract

Darier disease (DD) is a rare severe acantholytic skin disease caused by mutations in the ATP2A2 gene that encodes for the sarco/endoplasmic reticulum calcium ATPase isoform 2 (SERCA2). SERCA2 maintains endoplasmic reticulum calcium homeostasis by pumping calcium into the ER, critical for regulating cellular calcium dynamics and cellular function. To date, there is no treatment that specifically targets the disease mechanisms in DD. Dantrolene sodium (Dl) is a ryanodine receptor antagonist that inhibits calcium release from ER to increase ER calcium levels and is currently used for non-dermatological indications. In this study, we first identified dysregulated genes and molecular pathways in DD patient skin, demonstrating downregulation of cell adhesion and calcium homeostasis pathways, as well as upregulation of ER stress and apoptosis. We then show in various in vitro models of DD and SERCA2 inhibition that Dl aided in the retention of ER calcium and promoted cell adhesion. In addition, Dl treatment reduced ER stress and suppressed apoptosis. Our findings suggest that Dl specifically targets pathogenic mechanisms of DD and may be a potential treatment.

Indexed as

CalciumDantroleneDarier DiseaseSarcoplasmic Reticulum Calcium-Transporting ATPasesApoptosisCell AdhesionEndoplasmic ReticulumEndoplasmic Reticulum StressHumansSkinATP2A2 protein, humanCalciumDantroleneSarcoplasmic Reticulum Calcium-Transporting ATPasesCell AdhesionDantroleneDarier DiseaseER CalciumUPR

Identifiers

PMID39060641
PMCPMC11392931

What Socratic holds

Textmetadata
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 Socratic graph.