ArticleThe Journal of clinical investigation2017
Targeting deregulated AMPK/mTORC1 pathways improves muscle function in myotonic dystrophy type I.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Protein Phosphorylation Alterations in Myotonic Dystrophy Type 1: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Impaired Myogenic Differentiation Is a Shared Feature Across Genetic Myopathies.International journal of molecular sciences · 2026Review
- Current biomarker development in myotonic dystrophies.Journal of neurology · 2026Review
- Commitment to Myogenic Differentiation Significantly Aggravates the RNA Phenotype in Myotonic Dystrophy Type 1.Neuropathology and applied neurobiology · 2026Article
- 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
- Multiple Defects in Muscle Regeneration in the HSALR Mouse Model of RNA Toxicity.International journal of molecular sciences · 2025Article
- HSAInternational journal of molecular sciences · 2025Article
- Molecular genetics of myotonic dystrophy and the evolution of therapeutic approaches.Journal of human genetics · 2025Review
- Multisystem Symptoms in Myotonic Dystrophy Type 1: A Management and Therapeutic Perspective.International journal of molecular sciences · 2025Review
- The role of CNBP in brain atrophy and its targeting in myotonic dystrophy type 2.Human molecular genetics · 2025Article
- New Horizons in Myotonic Dystrophy Type 1: Cellular Senescence as a Therapeutic Target.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Alternative splicing dysregulation across tissue and therapeutic approaches in a mouse model of myotonic dystrophy type 1.Molecular therapy. Nucleic acids · 2024Article
- Article
- CaMKIIβ deregulation contributes to neuromuscular junction destabilization in Myotonic Dystrophy type I.Skeletal muscle · 2024Article
- Therapeutic potential of oleic acid supplementation in myotonic dystrophy muscle cell models.Biological research · 2024Article
- MYTHO is a novel regulator of skeletal muscle autophagy and integrity.Nature communications · 2023Article
- Pluripotent Stem Cells in Disease Modeling and Drug Discovery for Myotonic Dystrophy Type 1.Cells · 2023Review
- Polyadenylate-binding protein cytoplasmic 1 mediates alternative splicing events of immune-related genes in gastric cancer cells.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- Article
- Development of Therapeutic Approaches for Myotonic Dystrophies Type 1 and Type 2.International journal of molecular sciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Myotonic dystrophy type I (DM1) is a disabling multisystemic disease that predominantly affects skeletal muscle. It is caused by expanded CTG repeats in the 3'-UTR of the dystrophia myotonica protein kinase (DMPK) gene. RNA hairpins formed by elongated DMPK transcripts sequester RNA-binding proteins, leading to mis-splicing of numerous pre-mRNAs. Here, we have investigated whether DM1-associated muscle pathology is related to deregulation of central metabolic pathways, which may identify potential therapeutic targets for the disease. In a well-characterized mouse model for DM1 (HSALR mice), activation of AMPK signaling in muscle was impaired under starved conditions, while mTORC1 signaling remained active. In parallel, autophagic flux was perturbed in HSALR muscle and in cultured human DM1 myotubes. Pharmacological approaches targeting AMPK/mTORC1 signaling greatly ameliorated muscle function in HSALR mice. AICAR, an AMPK activator, led to a strong reduction of myotonia, which was accompanied by partial correction of misregulated alternative splicing. Rapamycin, an mTORC1 inhibitor, improved muscle relaxation and increased muscle force in HSALR mice without affecting splicing. These findings highlight the involvement of AMPK/mTORC1 deregulation in DM1 muscle pathophysiology and may open potential avenues for the treatment of this disease.
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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.