ArticlePLoS genetics2022
Activation of the ubiquitin-proteasome system contributes to oculopharyngeal muscular dystrophy through muscle atrophy.
Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Emerging roles of microRNAs and other non-coding transcriptome in muscular dystrophies.Inflammation and regeneration · 2026Review
- Exercise preconditioning prevents immobilization-induced skeletal muscle atrophy by activating Prmt1-p38/ATF2-Sesn1 signaling axis in C57BL/6J mice.Sports medicine and health science · 2026Article
- Article
- Insights into the heterogeneity of oculopharyngeal muscular dystrophy.Neurogenetics · 2025Article
- Nuclear Protein Aggregates Disrupt RNA Processing and Alter Biomechanics in a Muscle Cell Model of OPMD.Aging and disease · 2025Article
- Polyalanine Expansion in PABPN1 Alters the Structure and Dynamics of Its Nuclear Aggregates in Differentiated Muscle Cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Astragaloside IV Improves Muscle Atrophy by Modulating the Activity of UPS and ALP via Suppressing Oxidative Stress and Inflammation in Denervated Mice.Molecular neurobiology · 2025Article
- Review
- Exploring the Intersection of Diabetes and Musculoskeletal Health : Diabetes and Musculoskeletal Health.Galen medical journal · 2025Review
- Decoding Nucleotide Repeat Expansion Diseases: Novel Insights fromInternational journal of molecular sciences · 2024Review
- Experience-dependent Tip60 nucleocytoplasmic transport is regulated by its NLS/NES sequences for neuroplasticity gene control.Molecular and cellular neurosciences · 2023Article
- Genomic selection pressure discovery using site-frequency spectrum and reduced local variability statistics in Pakistani Dera-Din-Panah goat.Tropical animal health and production · 2023Article
- Chemotherapy induces cell plasticity; controlling plasticity increases therapeutic response.Signal transduction and targeted therapy · 2023Article
- Asynchronous transcription and translation of neurotransmitter-related genes characterize the initial stages of neuronal maturation in Drosophila.PLoS biology · 2023Article
- Drosophila Models Reveal Properties of Mutant Lamins That Give Rise to Distinct Diseases.Cells · 2023Article
- The small compound Icerguastat reduces muscle defects in oculopharyngeal muscular dystrophy through the PERK pathway of the unfolded protein response.Open biology · 2023Article
- The phenotypic and genotypic features of Chinese patients with oculopharyngeal muscular dystrophy.Annals of clinical and translational neurology · 2023Article
- Assessment of PABPN1 nuclear inclusions on a large cohort of patients and in a human xenograft model of oculopharyngeal muscular dystrophy.Acta neuropathologica · 2022Article
- Exogenous Antioxidants in Remyelination and Skeletal Muscle Recovery.Biomedicines · 2022Review
- Clinical and mechanism advances of neuronal intranuclear inclusion disease.Frontiers in aging neuroscience · 2022Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oculopharyngeal muscular dystrophy (OPMD) is a late-onset disorder characterized by progressive weakness and degeneration of specific muscles. OPMD is due to extension of a polyalanine tract in poly(A) binding protein nuclear 1 (PABPN1). Aggregation of the mutant protein in muscle nuclei is a hallmark of the disease. Previous transcriptomic analyses revealed the consistent deregulation of the ubiquitin-proteasome system (UPS) in OPMD animal models and patients, suggesting a role of this deregulation in OPMD pathogenesis. Subsequent studies proposed that UPS contribution to OPMD involved PABPN1 aggregation. Here, we use a Drosophila model of OPMD to address the functional importance of UPS deregulation in OPMD. Through genome-wide and targeted genetic screens we identify a large number of UPS components that are involved in OPMD. Half dosage of UPS genes reduces OPMD muscle defects suggesting a pathological increase of UPS activity in the disease. Quantification of proteasome activity confirms stronger activity in OPMD muscles, associated with degradation of myofibrillar proteins. Importantly, improvement of muscle structure and function in the presence of UPS mutants does not correlate with the levels of PABPN1 aggregation, but is linked to decreased degradation of muscle proteins. Oral treatment with the proteasome inhibitor MG132 is beneficial to the OPMD Drosophila model, improving muscle function although PABPN1 aggregation is enhanced. This functional study reveals the importance of increased UPS activity that underlies muscle atrophy in OPMD. It also provides a proof-of-concept that inhibitors of proteasome activity might be an attractive pharmacological approach for OPMD.
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