ArticleHuman molecular genetics2014
High-content screening identifies small molecules that remove nuclear foci, affect MBNL distribution and CELF1 protein levels via a PKC-independent pathway in myotonic dystrophy cell lines.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Curriculum vitae of CUG binding protein 1 (CELF1) in homeostasis and diseases: a systematic review.Cellular & molecular biology letters · 2024Pooled it
- Therapeutic Strategies Targeting the Molecular Pathogenesis of Myotonic Dystrophy Type 1: Current Status and Future Directions.Molecular diagnosis & therapy · 2026Review
- Targeting Expanded CUG and CTG Repeats as a Therapeutic Approach for Myotonic Dystrophy Type 1 (DM1).ChemMedChem · 2026Review
- Disruptions of cell signaling pathways in myotonic dystrophy type 1 skeletal muscle, their pathogenic impact, and potential for combinatorial therapeutics.The Journal of biological chemistry · 2026Review
- miR-107 repressesMolecular therapy. Nucleic acids · 2025Article
- Characterization ofNAR molecular medicine · 2025Article
- Functions of the Muscleblind-like protein family and their role in disease.Cell communication and signaling : CCS · 2025Review
- Small Molecule Screening Identifies HSP90 as a Modifier of RNA Foci in Myotonic Dystrophy Type 1.Molecular and cellular biology · 2025Article
- Non-Mammalian Models for Understanding Neurological Defects in RASopathies.Biomedicines · 2024Review
- Cellular and Genomic Features of Muscle Differentiation from Isogenic Fibroblasts and Myoblasts.Cells · 2023Article
- Modeling Human Muscular Dystrophies in Zebrafish: Mutant Lines, Transgenic Fluorescent Biosensors, and Phenotyping Assays.International journal of molecular sciences · 2023Review
- Vorinostat Improves Myotonic Dystrophy Type 1 Splicing Abnormalities in DM1 Muscle Cell Lines and Skeletal Muscle from a DM1 Mouse Model.International journal of molecular sciences · 2023Article
- Pluripotent Stem Cells in Disease Modeling and Drug Discovery for Myotonic Dystrophy Type 1.Cells · 2023Review
- Development of Therapeutic Approaches for Myotonic Dystrophies Type 1 and Type 2.International journal of molecular sciences · 2022Review
- Molecular Therapies for Myotonic Dystrophy Type 1: From Small Drugs to Gene Editing.International journal of molecular sciences · 2022Review
- Disrupting the Molecular Pathway in Myotonic Dystrophy.International journal of molecular sciences · 2021Review
- Brain Pathogenesis and Potential Therapeutic Strategies in Myotonic Dystrophy Type 1.Frontiers in aging neuroscience · 2021Review
- Article
- A CTG repeat-selective chemical screen identifies microtubule inhibitors as selective modulators of toxic CUG RNA levels.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- An Overview of Circular RNAs and Their Implications in Myotonic Dystrophy.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 3 countries.
Funding
Abstract
Myotonic dystrophy (DM) is a multi-system neuromuscular disorder for which there is no treatment. We have developed a medium throughput phenotypic assay, based on the identification of nuclear foci in DM patient cell lines using in situ hybridization and high-content imaging to screen for potentially useful therapeutic compounds. A series of further assays based on molecular features of DM have also been employed. Two compounds that reduce and/or remove nuclear foci have been identified, Ro 31-8220 and chromomycin A3. Ro 31-8220 is a PKC inhibitor, previously shown to affect the hyperphosphorylation of CELF1 and ameliorate the cardiac phenotype in a DM1 mouse model. We show that the same compound eliminates nuclear foci, reduces MBNL1 protein in the nucleus, affects ATP2A1 alternative splicing and reduces steady-state levels of CELF1 protein. We demonstrate that this effect is independent of PKC activity and conclude that this compound may be acting on alternative kinase targets within DM pathophysiology. Understanding the activity profile for this compound is key for the development of targeted therapeutics in the treatment of DM.
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Registered trials
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.