ArticleScience (New York, N.Y.)2014
C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins.
Article in Science (New York, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 489 papers, 1 of them a synthesis that pooled it.
What it found
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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
489 citing papers in PubMed, 1 synthesis or guideline pooled it, 760 citations in OpenAlex.
- Elucidating the Role of Cerebellar Synaptic Dysfunction in C9orf72-ALS/FTD - a Systematic Review and Meta-Analysis.Cerebellum (London, England) · 2022Pooled it
- Altered neuronal start codon stringency favors cap-independent repeat-associated non-AUG translation.Nucleic acids research · 2026Article
- Technologies for engineering repetitive DNA.Quantitative biology (Beijing, China) · 2026Review
- The Prospective Regulatory Functions of lncRNAs and Their ceRNA Networks in the Development of Motor Neurons and Associated Diseases.Biomolecules · 2026Review
- RAN Translation-Coupled Decay of theInternational journal of molecular sciences · 2026Article
- Glial cell toxicity in a Drosophila C9orf72 neurodegeneration model.PLoS genetics · 2026Article
- Altered neuronal start codon stringency favors cap-independent repeat-associated non-AUG translation.bioRxiv : the preprint server for biology · 2026Article
- Karyoptosis mediates cell death and neurodegeneration upon proteotoxic stress.Nature communications · 2026Article
- Microglial Dysfunction Induced by C9ORF72 Dipeptide Repeat Proteins: Biomarker and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Environmental Factors Drive Neurodegenerative Diseases Through Glutamate Excitotoxicity: A Convergent Mechanistic Pathway.Neuroscience bulletin · 2026Review
- The intrinsic disorder challenge for AlphaFold: A case study of G3BP1 and pathogenic peptide.iScience · 2026Article
- Targeting the integrated stress response or Ataxin-2 alleviates neurodegeneration in PolyGR models of C9orf72 associated frontotemporal dementia and amyotrophic lateral sclerosis.Acta neuropathologica communications · 2026Article
- Intracellular Aβ42 Sequestration by a Serine Protease Mitigates Neurotoxicity in a Drosophila Alzheimer's Disease Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Direct targeting of C9ORF72 repeat RNA with fluorinated antisense oligonucleotides.Nucleic acids research · 2026Article
- Microprotein Regulates G-quadruplex Driven RNA Aggregation.bioRxiv : the preprint server for biology · 2026Article
- Condensate protein aggregation in ALS/FTD is regulated by GGGGCC-repeat RNA scaffolds.Nature structural & molecular biology · 2026Article
- Surface glia for modeling ALS-FTD-associated mutant C9orf72 toxicity in the nervous system ofGenes & diseases · 2026Article
- Genetically Modified Primate Models for Brain Disorder Research.Neuroscience bulletin · 2026Review
- Increased neuronal activity restores circadian function in Drosophila models of C9orf72-ALS/FTD.iScience · 2026Article
- Antisense Dipeptide Repeat Proteins Drive Widescale Purine Metabolism Aberration inInternational journal of molecular sciences · 2026Article
429 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 2 institutions in 2 countries.
Funding
Abstract
An expanded GGGGCC repeat in C9orf72 is the most common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis. A fundamental question is whether toxicity is driven by the repeat RNA itself and/or by dipeptide repeat proteins generated by repeat-associated, non-ATG translation. To address this question, we developed in vitro and in vivo models to dissect repeat RNA and dipeptide repeat protein toxicity. Expression of pure repeats, but not stop codon-interrupted "RNA-only" repeats in Drosophila caused adult-onset neurodegeneration. Thus, expanded repeats promoted neurodegeneration through dipeptide repeat proteins. Expression of individual dipeptide repeat proteins with a non-GGGGCC RNA sequence revealed that both poly-(glycine-arginine) and poly-(proline-arginine) proteins caused neurodegeneration. These findings are consistent with a dual toxicity mechanism, whereby both arginine-rich proteins and repeat RNA contribute to C9orf72-mediated neurodegeneration.
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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.