PuSH - Publikationsserver des Helmholtz Zentrums München: High-content screen identifies cyclosporin A as a novel ABCA3-specific molecular corrector.

Informationen

Hinweise zu Qualitätskriterien von Zeitschriften

Open-Access-Richtlinie der Helmholtz-Gemeinschaft 2016

CC Licencences

Metriken für Publikationen

Navigation

Startseite

English

EVA: Veröffentlichen

Neuer EVA Antrag

Recherche

Erweiterte Suche

Durchblättern nach ...

... HMGU-Autoren/Konsortien

... Organisationsstruktur

... Zeitschriften

... Publikationstypen

... Forschungsdaten

... Arbeitsgruppen

... Erscheinungsjahr

Publikationen im Überblick

Statistik

HGF Fortschrittsbericht

OA Publikationen

Eintragen

Neue Publikation eintragen

Neue Publikation holen aus...

...EVA

Fehlende Publikation melden

Highlights

Suche

Hilfe & Kontakt

Ansprechpartner

Hilfe

Datenschutz

Helmholtz Open Science

Bibliometrische Indikatoren

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Forstner, M.* ; Lin, S. ; Yang, X.* ; Kinting, S.* ; Rothenaigner, I. ; Schorpp, K.K. ; Li, Y.* ; Hadian, K. ; Griese, M.*

High-content screen identifies cyclosporin A as a novel ABCA3-specific molecular corrector.

Am. J. Respir. Cell Mol. Biol. 66, 382-390 (2022)

Verlagsversion

Postprint

DOI

PMC

	Open Access Green

Abstract
Metriken
Zusatzinfos

ATP-binding cassette (ABC) subfamily A member 3 (ABCA3) is a lipid transporter expressed in alveolar type II cells and localized in the limiting membrane of lamellar bodies. It is crucial for pulmonary surfactant storage and homeostasis. Mutations in the ABCA3 gene are the most common genetic cause of respiratory distress syndrome in mature newborns and interstitial lung disease in children. Apart from lung transplantation, there is no cure available. To address the lack of causal therapeutic options for ABCA3 deficiency, a rapid and reliable approach is needed to investigate variant-specific molecular mechanisms and to identify pharmacological modulators for mono- or combination therapies. To this end, we developed a phenotypic cell-based assay to autonomously identify ABCA3 wild-type-like or mutant-like cells by using machine-learning algorithms aimed at identifying morphological differences in WT and mutant cells. The assay was subsequently used to identify new drug candidates for ABCA3 specific molecular correction by high-content screening of 1,280 food and drug administration-approved small molecules. Cyclosporin A (CsA) was identified as a potent corrector, specific for some, but not all ABCA3 variants. Results were validated by our previously established functional small format assays. Hence, CsA may be selected for orphan drug evaluation in controlled repurposing trials in patients.

Impact Factor

Scopus SNIP

Scopus
Cited By

Altmetric

7.748

1.181