ArticleNeuron2014
Antisense proline-arginine RAN dipeptides linked to C9ORF72-ALS/FTD form toxic nuclear aggregates that initiate in vitro and in vivo neuronal death.
Article in Neuron, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 361 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.
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Who cites it
361 citing papers in PubMed, 1 synthesis or guideline pooled it, 554 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
- Two dipeptide repeat proteins are produced from mammalian telomeric RNA previously thought to be a long non-coding RNA.RNA biology · 2026Review
- PAICS mediates DNA damage and cerebellar neuronal loss in C9orf72 amyotrophic lateral sclerosis.Brain : a journal of neurology · 2026Article
- Cell Death in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- Glial cell toxicity in a Drosophila C9orf72 neurodegeneration model.PLoS genetics · 2026Article
- Convergent nuclear proteostasis alterations across 40S ribosomal protein deficiencies.Nature communications · 2026Article
- Nuclear condensates formed by truncated mutant NEK1s impede ribosomal RNA biogenesis and drive motor dysfunction.Nature communications · 2026Article
- Microglial Dysfunction Induced by C9ORF72 Dipeptide Repeat Proteins: Biomarker and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Genetically Modified Primate Models for Brain Disorder Research.Neuroscience bulletin · 2026Review
- Antisense Dipeptide Repeat Proteins Drive Widescale Purine Metabolism Aberration inInternational journal of molecular sciences · 2026Article
- Blocking RAN translation without altering repeat RNAs rescuesScience (New York, N.Y.) · 2026Article
- Protein tandem repeats that produce frameshifts can generate new structural states and functions.The FEBS journal · 2026Article
- Article
- Nucleolar aggregation of key neuropathological proteins in the postmortem neurodegenerative brain.Acta neuropathologica · 2025Article
- The molecular mechanism of uptake and cell-to-cell transmission of arginine-containing dipeptide repeat proteins.bioRxiv : the preprint server for biology · 2025Article
- The telomeric valine-arginine dipeptide repeat protein changes state to diffuse staining in mitosis and represses in vitro translation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- C9orf72 ALS-causing mutations lead to mislocalization and aggregation of nucleoporin Nup107 into stress granules.FEBS letters · 2025Article
- Glial cell-intrinsic and non-cell autonomous toxicity in a Drosophila C9orf72 neurodegeneration model.bioRxiv : the preprint server for biology · 2025Article
- Inhibition of PolyGA Dipeptide Repeat Protein Aggregation by Nucleic Acid Aptamers in C9 Amyotrophic Lateral Sclerosis-Frontotemporal Dementia Models.Molecular neurobiology · 2025Article
- Optimizing the in vitro neuronal microenvironment to mitigate phototoxicity in live-cell imaging.Stem cell research & therapy · 2025Article
301 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Expanded GGGGCC (G4C2) nucleotide repeats within the C9ORF72 gene are the most common genetic mutation associated with both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Sense and antisense transcripts of these expansions are translated to form five dipeptide repeat proteins (DRPs). We employed primary cortical and motor neuron cultures, live-cell imaging, and transgenic fly models and found that the arginine-rich dipeptides, in particular Proline-Arginine (PR), are potently neurotoxic. Factors that anticipated their neurotoxicity included aggregation in nucleoli, decreased number of processing bodies, and stress granule formation, implying global translational dysregulation as path accountable for toxicity. Nuclear PR aggregates were also found in human induced motor neurons and postmortem spinal cord tissues from C9ORF72 ALS and ALS/FTD patients. Intronic G4C2 transcripts, but not loss of C9ORF72 protein, are also toxic to motor and cortical neurons. Interestingly, G4C2 transcript-mediated neurotoxicity synergizes with that of PR aggregates, suggesting convergence of mechanisms.
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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.