ArticleAnnals of neurology2018
Dysfunctional sarcomere contractility contributes to muscle weakness in ACTA1-related nemaline myopathy (NEM3).
Article in Annals of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 35 citations in OpenAlex.
- Age-related changes in adrenergic regulation of contractility and redox status of glycolytic and oxidative skeletal muscles.GeroScience · 2026Article
- The D2.B10-DmdThe American journal of pathology · 2026Article
- Molecular Bases of Myopathies and Their Impact on Clinical Practice: Advances and Future Perspectives.International journal of molecular sciences · 2026Review
- Fine-tuning striated muscle performance: conserved sarcomere-level mechanisms across insect and vertebrate systems.Frontiers in physiology · 2026Review
- Retrospective Cohort Analysis of Clinical, Molecular, and Histopathologic Characteristics of 275 Patients With Nemaline Myopathy.Neurology. Genetics · 2025Article
- Pathogenic TNNT1 variants are associated with aberrant thin filament compliance and myofibre hyper-contractility.The Journal of physiology · 2025Article
- Congenital myopathies: pathophysiological mechanisms and promising therapies.Journal of translational medicine · 2024Review
- Differences in thick filament activation in fast rodent skeletal muscle and slow porcine cardiac muscle.The Journal of physiology · 2024Article
- Tirasemtiv enhances submaximal muscle tension in an Acta1:p.Asp286Gly mouse model of nemaline myopathy.The Journal of general physiology · 2024Article
- An Update on Reported Variants in the Skeletal MuscleHuman mutation · 2024Review
- Case report: A novelFrontiers in neurology · 2024Article
- Article
- Pharmacological Inhibition of Myostatin in a Mouse Model of Typical Nemaline Myopathy Increases Muscle Size and Force.International journal of molecular sciences · 2023Article
- Different Mouse Models of Nemaline Myopathy Harboring Acta1 Mutations Display Differing Abnormalities Related to Mitochondrial Biology.The American journal of pathology · 2023Article
- Actin polymerization and depolymerization in developing vertebrates.Frontiers in physiology · 2023Review
- Article
- Removal of MuRF1 Increases Muscle Mass in Nemaline Myopathy Models, but Does Not Provide Functional Benefits.International journal of molecular sciences · 2022Article
- miR-1183 Is a Key Marker of Remodeling upon Stretch and Tachycardia in Human Myocardium.International journal of molecular sciences · 2022Article
- Clinico-pathological features and mutational spectrum of 16 nemaline myopathy patients from a Chinese neuromuscular center.Acta neurologica Belgica · 2022Article
- Small Angle X-ray Diffraction as a Tool for Structural Characterization of Muscle Disease.International journal of molecular sciences · 2022Review
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Authors and funding
18 authors at 8 institutions in 6 countries.
Funding
Abstract
objectiveNemaline myopathy (NM) is one of the most common congenital nondystrophic myopathies and is characterized by muscle weakness, often from birth. Mutations in ACTA1 are a frequent cause of NM (ie, NEM3). ACTA1 encodes alpha-actin 1, the main constituent of the sarcomeric thin filament. The mechanisms by which mutations in ACTA1 contribute to muscle weakness in NEM3 are incompletely understood. We hypothesized that sarcomeric dysfunction contributes to muscle weakness in NEM3 patients.
methodsTo test this hypothesis, we performed contractility measurements in individual muscle fibers and myofibrils obtained from muscle biopsies of 14 NEM3 patients with different ACTA1 mutations. To identify the structural basis for impaired contractility, low angle X-ray diffraction and stimulated emission-depletion microscopy were applied.
resultsOur findings reveal that muscle fibers of NEM3 patients display a reduced maximal force-generating capacity, which is caused by dysfunctional sarcomere contractility in the majority of patients, as revealed by contractility measurements in myofibrils. Low angle X-ray diffraction and stimulated emission-depletion microscopy indicate that dysfunctional sarcomere contractility in NEM3 patients involves a lower number of myosin heads binding to actin during muscle activation. This lower number is not the result of reduced thin filament length. Interestingly, the calcium sensitivity of force is unaffected in some patients, but decreased in others.
interpretationDysfunctional sarcomere contractility is an important contributor to muscle weakness in the majority of NEM3 patients. This information is crucial for patient stratification in future clinical trials. Ann Neurol 2018;83:269-282.
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