ArticleActa neuropathologica2013
Modeling key pathological features of frontotemporal dementia with C9ORF72 repeat expansion in iPSC-derived human neurons.
Article in Acta neuropathologica, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 204 papers.
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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.
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Who cites it
204 citing papers in PubMed, 324 citations in OpenAlex.
- Hippocampal sclerosis dementia with the C9ORF72 hexanucleotide repeat expansion.Neurobiology of aging · 2014Trial
- RAN proteins and RNA foci from antisense transcripts in C9ORF72 ALS and frontotemporal dementia.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- Modeling human neurodegeneration with iPSCs: opportunities, limitations, and the challenge of aging.The Journal of clinical investigation · 2026Review
- Global transcriptional changes across multiple isogeniciScience · 2026Article
- Direct targeting of C9ORF72 repeat RNA with fluorinated antisense oligonucleotides.Nucleic acids research · 2026Article
- Frontotemporal dementia patient-derived iPSC neurons show cell pathological hallmarks and evidence for synaptic dysfunction and DNA damage.Molecular psychiatry · 2026Article
- Blocking RAN translation without altering repeat RNAs rescuesScience (New York, N.Y.) · 2026Article
- Article
- RNA-Focused DNA-Encoded Library Construction, Screening, and Integration of Docking Identify Bioactive Ligands of Pathogenic r(GbioRxiv : the preprint server for biology · 2025Article
- Enhanced hybridization-proximity labeling discovers protein interactomes of single RNA molecules.Nature communications · 2025Article
- Inhibition of Salt-Inducible Kinase 2 Protects Motor Neurons From Degeneration in ALS by Activating Autophagic Flux and Enhancing mTORC1 Activity.CNS neuroscience & therapeutics · 2025Article
- Epg5 links proteotoxic stress due to defective autophagic clearance and epileptogenesis inAutophagy · 2025Article
- The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).Autophagy reports · 2025Review
- Early disruption of the CREB pathway drives dendritic morphological alterations in FTD/ALS cortical neurons.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- C9orf72-Associated Dipeptide Repeat Expansions Perturb ER-Golgi Vesicular Trafficking, Inducing Golgi Fragmentation and ER Stress, in ALS/FTD.Molecular neurobiology · 2024Article
- The exocyst subunit EXOC2 regulates the toxicity of expanded GGGGCC repeats in C9ORF72-ALS/FTD.Cell reports · 2024Article
- Generation of human iPSC-derived phrenic-like motor neurons to model respiratory motor neuron degeneration in ALS.Communications biology · 2024Article
- Mitochondria: A Promising Convergent Target for the Treatment of Amyotrophic Lateral Sclerosis.Cells · 2024Review
- A toxic gain-of-function mechanism in C9orf72 ALS impairs the autophagy-lysosome pathway in neurons.Acta neuropathologica communications · 2023Article
- Phenylalanine-tRNA aminoacylation is compromised by ALS/FTD-associated C9orf72 C4G2 repeat RNA.Nature communications · 2023Article
144 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
The recently identified GGGGCC repeat expansion in the noncoding region of C9ORF72 is the most common pathogenic mutation in patients with frontotemporal dementia (FTD) or amyotrophic lateral sclerosis (ALS). We generated a human neuronal model and investigated the pathological phenotypes of human neurons containing GGGGCC repeat expansions. Skin biopsies were obtained from two subjects who had >1,000 GGGGCC repeats in C9ORF72 and their respective fibroblasts were used to generate multiple induced pluripotent stem cell (iPSC) lines. After extensive characterization, two iPSC lines from each subject were selected, differentiated into postmitotic neurons, and compared with control neurons to identify disease-relevant phenotypes. Expanded GGGGCC repeats exhibit instability during reprogramming and neuronal differentiation of iPSCs. RNA foci containing GGGGCC repeats were present in some iPSCs, iPSC-derived human neurons and primary fibroblasts. The percentage of cells with foci and the number of foci per cell appeared to be determined not simply by repeat length but also by other factors. These RNA foci do not seem to sequester several major RNA-binding proteins. Moreover, repeat-associated non-ATG (RAN) translation products were detected in human neurons with GGGGCC repeat expansions and these neurons showed significantly elevated p62 levels and increased sensitivity to cellular stress induced by autophagy inhibitors. Our findings demonstrate that key neuropathological features of FTD/ALS with GGGGCC repeat expansions can be recapitulated in iPSC-derived human neurons and also suggest that compromised autophagy function may represent a novel underlying pathogenic mechanism.
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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.