ArticleHuman molecular genetics2014
Unveiling the degradative route of the V247M α-sarcoglycan mutant responsible for LGMD-2D.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Genotype-phenotype correlations in alpha-sarcoglycanopathy: a systematic review.Irish journal of medical science · 2022Pooled it
- AlphaMissense prediction for the evaluation of missense variants in the diagnostic setting of neuromuscular disorders.Journal of neuromuscular diseases · 2026Article
- Cytoplasmic region of beta-dystroglycan is essential for postsynaptic maturation and neuromuscular function in mice.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Repairing the defective folding of alpha-sarcoglycan is needed to promote myogenic cell engraftment in 3D artificial muscle models of LGMDR3.Skeletal muscle · 2025Article
- Review
- ELK1 inhibition alleviates amyloid pathology and memory decline by promoting the SYVN1-mediated ubiquitination and degradation of PS1 in Alzheimer's disease.Experimental & molecular medicine · 2025Article
- Efficacy of Cystic Fibrosis Transmembrane Regulator Corrector C17 in Beta-Sarcoglycanopathy-Assessment of Patient's Primary Myotubes.International journal of molecular sciences · 2024Article
- The missense mutation C667F in murine β-dystroglycan causes embryonic lethality, myopathy and blood-brain barrier destabilization.Disease models & mechanisms · 2024Article
- An evolutionarily conserved ubiquitin ligase drives infection and transmission of flaviviruses.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Modeling Sarcoglycanopathy inInternational journal of molecular sciences · 2023Article
- Synthesis and Evaluation of Bithiazole Derivatives As Potential α-Sarcoglycan Correctors.ACS medicinal chemistry letters · 2023Article
- The 2022 On-site Padua Days on Muscle and Mobility Medicine hosts the University of Florida Institute of Myology and the Wellstone Center, March 30 - April 3, 2022 at the University of Padua and Thermae of Euganean Hills, Padua, Italy: The collection of abstracts.European journal of translational myology · 2022Article
- CFTR corrector C17 is effective in muscular dystrophy, in vivo proof of concept in LGMDR3.Human molecular genetics · 2022Article
- Translational research on Myology and Mobility Medicine: 2021 semi-virtual PDM3 from Thermae of Euganean Hills, May 26 - 29, 2021.European journal of translational myology · 2021Article
- Genetic cause of heterogeneous inherited myopathies in a cohort of Greek patients.Molecular genetics and metabolism reports · 2020Article
- Combined Use of CFTR Correctors in LGMD2D Myotubes Improves Sarcoglycan Complex Recovery.International journal of molecular sciences · 2020Article
- Proteostasis Regulation in the Endoplasmic Reticulum: An Emerging Theme in the Molecular Pathology and Therapeutic Management of Familial Hypercholesterolemia.Frontiers in genetics · 2020Review
- Identification of thiostrepton as a pharmacological approach to rescue misfolded alpha-sarcoglycan mutant proteins from degradation.Scientific reports · 2019Article
- A molecular overview of the primary dystroglycanopathies.Journal of cellular and molecular medicine · 2019Review
- Collection of the Abstracts of the 2019Sp PMD: Translational Myology and Mobility Medicine.European journal of translational myology · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Many membrane and secretory proteins that fail to pass quality control in the endoplasmic reticulum (ER) are dislocated into the cytosol and degraded by the proteasome. In applying rigid rules, however, quality control sometimes discharges proteins that, even though defective, retain their function. The unnecessary removal of such proteins represents the pathogenetic hallmark of diverse genetic diseases, in the case of ΔF508 mutant of cystic fibrosis transmembrane conductance regulator being probably the best known example. Recently, the inappropriate proteasomal degradation of skeletal muscle sarcoglycans (α, β, γ and δ) with missense mutation has been proposed to be at the bases of mild-to-severe forms of limb girdle muscular dystrophy (LGMD) known as type 2D, 2E, 2C and 2F, respectively. The quality control pathway responsible for sarcoglycan mutant disposal, however, is so far unexplored. Here we reveal key components of the degradative route of V247M α-sarcoglycan mutant, the second most frequently reported mutation in LGMD-2D. The disclosure of the pathway, which is led by the E3 ligases HRD1 and RFP2, permits to identify new potential druggable targets of a disease for which no effective therapy is at present available. Notably, we show that the pharmacological inhibition of HRD1 activity rescues the expression of V247-α-sarcoglycan both in a heterologous cell model and in myotubes derived from a LGMD-2D patient carrying the L31P/V247M mutations. This represents the first evidence that the activity of E3 ligases, the enzymes in charge of mutant fate, can be eligible for drug interventions to treat sarcoglycanopathy.
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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.