ArticleActa neuropathologica2020
Intracellular calcium leak as a therapeutic target for RYR1-related myopathies.
Article in Acta neuropathologica, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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
32 citing papers in PubMed, 67 citations in OpenAlex.
- Structural basis for rosuvastatin-induced activation of skeletal muscle ryanodine receptor 1.Nature communications · 2026Article
- Ryanodine-1-Calstabin Complex Stabilizers in Antidoping Research: Synthesis, Metabolism, and Characterization.ChemPlusChem · 2026Article
- Structural basis for simvastatin-induced skeletal muscle weakness associated with type 1 ryanodine receptor T4709M mutation.The Journal of clinical investigation · 2025Article
- A review of recent studies on CRISPR/Cas9-mediated genome editing in a variety of muscle-related genetic disorders.Journal of translational medicine · 2025Review
- Dominant rhabdomyolysis linked to a recurrent ATP2A2 variant reducing SERCA2 function in muscle.Brain : a journal of neurology · 2025Article
- Universal Prime Editing Therapeutic Strategy for RyR1-Related Myopathies: A Protective Mutation Rescues Leaky RyR1 Channel.International journal of molecular sciences · 2025Article
- Dantrolene inhibition of ryanodine receptor 1 carrying the severe malignant hyperthermia mutation Y522S visualized by cryo-EM.Structure (London, England : 1993) · 2025Article
- Complementary Roles of Structure and Variant Effect Predictors in RyR1 Clinical Interpretation.Human mutation · 2025Article
- Myopathic manifestations across the adult lifespan of patients with malignant hyperthermia susceptibility: a narrative review.British journal of anaesthesia · 2024Review
- Congenital myopathies: pathophysiological mechanisms and promising therapies.Journal of translational medicine · 2024Review
- Article
- Spaceflight increases sarcoplasmic reticulum CaNPJ microgravity · 2024Article
- Molecular mechanisms and therapeutic strategies for neuromuscular diseases.Cellular and molecular life sciences : CMLS · 2024Review
- Rycal S48168 (ARM210) forEClinicalMedicine · 2024Article
- Article
- Long-term Natural History of Pediatric Dominant and RecessiveNeurology · 2023Article
- Function of a mutant ryanodine receptor (T4709M) linked to congenital myopathy.Scientific reports · 2023Article
- Targeting ryanodine receptors to treat human diseases.The Journal of clinical investigation · 2023Review
- RYR-1-Related Diseases International Research Workshop: From Mechanisms to Treatments Pittsburgh, PA, U.S.A., 21-22 July 2022.Journal of neuromuscular diseases · 2023Article
- Development of Ryanodine Receptor (RyR) Inhibitors for Skeletal Muscle and Heart Diseases.Juntendo Iji zasshi = Juntendo medical journal · 2023Article
Corrections and comments
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Authors and funding
27 authors at 6 institutions in 3 countries.
Funding
Abstract
RYR1 encodes the type 1 ryanodine receptor, an intracellular calcium release channel (RyR1) on the skeletal muscle sarcoplasmic reticulum (SR). Pathogenic RYR1 variations can destabilize RyR1 leading to calcium leak causing oxidative overload and myopathy. However, the effect of RyR1 leak has not been established in individuals with RYR1-related myopathies (RYR1-RM), a broad spectrum of rare neuromuscular disorders. We sought to determine whether RYR1-RM affected individuals exhibit pathologic, leaky RyR1 and whether variant location in the channel structure can predict pathogenicity. Skeletal muscle biopsies were obtained from 17 individuals with RYR1-RM. Mutant RyR1 from these individuals exhibited pathologic SR calcium leak and increased activity of calcium-activated proteases. The increased calcium leak and protease activity were normalized by ex-vivo treatment with S107, a RyR stabilizing Rycal molecule. Using the cryo-EM structure of RyR1 and a new dataset of > 2200 suspected RYR1-RM affected individuals we developed a method for assigning pathogenicity probabilities to RYR1 variants based on 3D co-localization of known pathogenic variants. This study provides the rationale for a clinical trial testing Rycals in RYR1-RM affected individuals and introduces a predictive tool for investigating the pathogenicity of RYR1 variants of uncertain significance.
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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.