ArticleThe American journal of pathology2010
Impaired autophagy in sporadic inclusion-body myositis and in endoplasmic reticulum stress-provoked cultured human muscle fibers.
Article in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 111 citations in OpenAlex.
- Mitophagy coordinates organelle crosstalk in health and diseases.Signal transduction and targeted therapy · 2026Review
- Case Report of an Atypical Presentation of Inclusion Body Myositis Masquerading as Polymyalgia Rheumatica.Current rheumatology reviews · 2026Article
- Mutual reinforcement of lymphotoxin-driven myositis and impaired autophagy in murine muscle.Brain : a journal of neurology · 2025Article
- The Role of C/EBP-Homologous Protein in Idiopathic Inflammatory Myopathies.Journal of cellular and molecular medicine · 2025Article
- Recent advances in the clinical spectrum and pathomechanisms associated with X-linked myopathy with excessive autophagy and otherJournal of neuromuscular diseases · 2025Review
- Cathepsin B Levels Correlate with the Severity of Canine Myositis.Biomolecules · 2025Article
- Idiopathic Inflammatory Myopathies: Recent Evidence Linking Pathogenesis and Clinical Features.International journal of molecular sciences · 2025Review
- NLRP3 Inflammasome Activation and Altered Mitophagy Are Key Pathways in Inclusion Body Myositis.Journal of cachexia, sarcopenia and muscle · 2025Article
- NLRP3 inflammasome activation and altered mitophagy are key pathways in inclusion body myositis.medRxiv : the preprint server for health sciences · 2024Article
- Sporadic Inclusion Body Myositis at the Crossroads between Muscle Degeneration, Inflammation, and Aging.International journal of molecular sciences · 2024Review
- Mitochondrial defects in sporadic inclusion body myositis-causes and consequences.Frontiers in cell and developmental biology · 2024Review
- Urine proteomics by mass spectrometry identifies proteins involved in key pathogenic pathways in patients with juvenile dermatomyositis.Rheumatology (Oxford, England) · 2023Article
- Protein Aggregates and Aggrephagy in Myopathies.International journal of molecular sciences · 2023Review
- The phenotypic and genotypic features of Chinese patients with oculopharyngeal muscular dystrophy.Annals of clinical and translational neurology · 2023Article
- Endoplasmic Reticulum Stress Is Involved in Muscular Pathogenesis in Idiopathic Inflammatory Myopathies.Frontiers in cell and developmental biology · 2022Article
- Autoantibodies in the pathogenesis of idiopathic inflammatory myopathies: Does the endoplasmic reticulum stress response have a role?Frontiers in immunology · 2022Review
- Autophagy in major human diseases.The EMBO journal · 2021Review
- Autophagy and Tau Protein.International journal of molecular sciences · 2021Review
- Review
- Programmed Cell Death Pathways in the Pathogenesis of Idiopathic Inflammatory Myopathies.Frontiers in immunology · 2021Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The hallmark pathologies of sporadic inclusion-body myositis (s-IBM) muscle fibers are autophagic vacuoles and accumulation of ubiquitin-positive multiprotein aggregates that contain amyloid-beta or phosphorylated tau in a beta-pleated sheet amyloid configuration. Endoplasmic reticulum stress (ERS) and 26S proteasome inhibition, also associated with s-IBM, putatively aggrandize the accumulation of misfolded proteins. However, autophagosomal-lysosomal pathway formation and function, indicated by autophagosome maturation, have not been previously analyzed in this system. Here we studied the autophagosomal-lysosomal pathway using 14 s-IBM and 30 disease control and normal control muscle biopsy samples and our cultured human muscle fibers in a microenvironment modified to resemble aspects of s-IBM pathology. We report for the first time that in s-IBM, lysosomal enzyme activities of cathepsin D and B were decreased 60% (P < 0.01) and 40% (P < 0.05), respectively. We also detected two indicators of increased autophagosome maturation, the presence of LC3-II and decreased mammalian target of rapamycin-mediated phosphorylation of p70S6 kinase. Moreover, in cultured human muscle fibers, ERS induction significantly decreased activities of cathepsins D and B, increased levels of LC3-II, decreased phosphorylation of p70S6 kinase, and decreased expression of VMA21, a chaperone for assembly of lysosomal V-ATPase. We conclude that in s-IBM muscle, decreased lysosomal proteolytic activity might enhance accumulation of misfolded proteins, despite increased maturation of autophagosomes, and that ERS is a possible cause of s-IBM-impaired lysosomal function. Thus, unblocking protein degradation in s-IBM muscle fibers may be a desirable therapeutic strategy.
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