ArticleEMBO molecular medicine2011
Antiprion drugs 6-aminophenanthridine and guanabenz reduce PABPN1 toxicity and aggregation in oculopharyngeal muscular dystrophy.
Article in EMBO molecular medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- The unfolded protein response in amyotrophic later sclerosis: results of a phase 2 trial.Brain : a journal of neurology · 2021Trial
- Protein misfolding, amyotrophic lateral sclerosis and guanabenz: protocol for a phase II RCT with futility design (ProMISe trial).BMJ open · 2017Trial
- The genetic and clinical characteristics of oculopharyngeal muscular dystrophy patients in Israel.Orphanet journal of rare diseases · 2026Article
- Mammalian integrated stress responses in stressed organelles and their functions.Acta pharmacologica Sinica · 2024Review
- New clinical insight in amyotrophic lateral sclerosis and innovative clinical development from the non-profit repurposing trial of the old drug guanabenz.Frontiers in medicine · 2024Review
- The small compound Icerguastat reduces muscle defects in oculopharyngeal muscular dystrophy through the PERK pathway of the unfolded protein response.Open biology · 2023Article
- Activation of the ubiquitin-proteasome system contributes to oculopharyngeal muscular dystrophy through muscle atrophy.PLoS genetics · 2022Article
- Anti-prion Drugs Targeting the Protein Folding Activity of the Ribosome Reduce PABPN1 Aggregation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Chaperna: linking the ancient RNA and protein worlds.RNA biology · 2021Review
- A Promising Future for Stem-Cell-Based Therapies in Muscular Dystrophies-In Vitro and In Vivo Treatments to Boost Cellular Engraftment.International journal of molecular sciences · 2019Review
- RNA-Based Therapy Utilizing Oculopharyngeal Muscular Dystrophy Transcript Knockdown and Replacement.Molecular therapy. Nucleic acids · 2019Article
- Molecular targets for modulating the protein translation vital to proteostasis and neuron degeneration in Parkinson's disease.Translational neurodegeneration · 2019Review
- PABPN1 gene therapy for oculopharyngeal muscular dystrophy.Nature communications · 2017Article
- The double life of the ribosome: When its protein folding activity supports prion propagation.Prion · 2017Review
- Protein Folding Activity of the Ribosome is involved in Yeast Prion Propagation.Scientific reports · 2016Article
- Article
- Prion 2016 Oral Abstracts.Prion · 2016Article
- Mitochondrial dysfunction reveals the role of mRNA poly(A) tail regulation in oculopharyngeal muscular dystrophy pathogenesis.PLoS genetics · 2015Article
- Hip flexion weakness is associated with impaired mobility in oculopharyngeal muscular dystrophy: a retrospective study with implications for trial design.Neuromuscular disorders : NMD · 2015Article
- Endoplasmic reticulum stress and oxidative stress in cell fate decision and human disease.Antioxidants & redox signaling · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset syndrome characterized by progressive degeneration of specific muscles. OPMD is caused by extension of a polyalanine tract in poly(A) binding protein nuclear 1 (PABPN1). Insoluble nuclear inclusions form in diseased muscles. We have generated a Drosophila model of OPMD that recapitulates the features of the disorder. Here, we show that the antiprion drugs 6-aminophenanthridine (6AP) and guanabenz acetate (GA), which prevent formation of amyloid fibers by prion proteins in cell models, alleviate OPMD phenotypes in Drosophila, including muscle degeneration and nuclear inclusion formation. The large ribosomal RNA and its activity in protein folding were recently identified as a specific cellular target of 6AP and GA. We show that deletions of the ribosomal DNA locus reduce OPMD phenotypes and act synergistically with sub-effective doses of 6AP. In a complementary approach, we demonstrate that ribosomal RNA accelerates in vitro fibril formation of PABPN1 N-terminal domain. These results reveal the conserved role of ribosomal RNA in different protein aggregation disorders and identify 6AP and GA as general anti-aggregation molecules.
Indexed as
Identifiers
What OpenQuestion holds
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.