ArticlePloS one2014
Allele-specific knockdown of ALS-associated mutant TDP-43 in neural stem cells derived from induced pluripotent stem cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 48 citations in OpenAlex.
- TDP-43 Aggregation: The Healthy-Toxic Balance of the Prion-Like Domain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- A Perspective on the Role of Mitochondrial Biomolecular Condensates (mtBCs) in Neurodegenerative Diseases and Evolutionary Links to Bacterial BCs.International journal of molecular sciences · 2025Review
- Targets and Gene Therapy of ALS (Part 1).International journal of molecular sciences · 2025Review
- Gene therapy breakthroughs in ALS: a beacon of hope for 20% of ALS patients.Translational neurodegeneration · 2025Review
- Lysosomal Dysfunction in Amyotrophic Lateral Sclerosis: A Familial Case Linked to the p.G376DInternational journal of molecular sciences · 2025Article
- Gene therapy for CNS disorders: modalities, delivery and translational challenges.Nature reviews. Neuroscience · 2024Review
- An ALS-associated mutation dysregulates microglia-derived extracellular microRNAs in a sex-specific manner.Disease models & mechanisms · 2024Article
- Desloratadine alleviates ALS-like pathology in hSOD1Acta pharmacologica Sinica · 2024Article
- Limbic-predominant age-related TDP43 encephalopathy (LATE) neuropathological change in neurodegenerative diseases.Nature reviews. Neurology · 2023Review
- Gene Therapy in Amyotrophic Lateral Sclerosis.Cells · 2022Review
- Allele-specific silencing as therapy for familial amyotrophic lateral sclerosis caused by the p.G376DBrain communications · 2022Article
- Combating deleterious phase transitions in neurodegenerative disease.Biochimica et biophysica acta. Molecular cell research · 2021Review
- Trends in Understanding the Pathological Roles of TDP-43 and FUS Proteins.Advances in experimental medicine and biology · 2021Article
- The Impact of ALS-Associated GenesCells · 2020Article
- From basic research to the clinic: innovative therapies for ALS and FTD in the pipeline.Molecular neurodegeneration · 2020Review
- Allele-specific genome targeting in the development of precision medicine.Theranostics · 2020Review
- Dysregulation of TDP-43 intracellular localization and early onset ALS are associated with a TARDBP S375G variant.Brain pathology (Zurich, Switzerland) · 2019Article
- ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now?Frontiers in neuroscience · 2019Review
- Mutant UBQLN2 promotes toxicity by modulating intrinsic self-assembly.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Prion-like properties of disease-relevant proteins in amyotrophic lateral sclerosis.Journal of neural transmission (Vienna, Austria : 1996) · 2018Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 4 countries.
Funding
Abstract
TDP-43 is found in cytoplasmic inclusions in 95% of amyotrophic lateral sclerosis (ALS) and 60% of frontotemporal lobar degeneration (FTLD). Approximately 4% of familial ALS is caused by mutations in TDP-43. The majority of these mutations are found in the glycine-rich domain, including the variant M337V, which is one of the most common mutations in TDP-43. In order to investigate the use of allele-specific RNA interference (RNAi) as a potential therapeutic tool, we designed and screened a set of siRNAs that specifically target TDP-43(M337V) mutation. Two siRNA specifically silenced the M337V mutation in HEK293T cells transfected with GFP-TDP-43(wt) or GFP-TDP-43(M337V) or TDP-43 C-terminal fragments counterparts. C-terminal TDP-43 transfected cells show an increase of cytosolic inclusions, which are decreased after allele-specific siRNA in M337V cells. We then investigated the effects of one of these allele-specific siRNAs in induced pluripotent stem cells (iPSCs) derived from an ALS patient carrying the M337V mutation. These lines showed a two-fold increase in cytosolic TDP-43 compared to the control. Following transfection with the allele-specific siRNA, cytosolic TDP-43 was reduced by 30% compared to cells transfected with a scrambled siRNA. We conclude that RNA interference can be used to selectively target the TDP-43(M337V) allele in mammalian and patient cells, thus demonstrating the potential for using RNA interference as a therapeutic tool for ALS.
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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.