ArticleProceedings of the National Academy of Sciences of the United States of America2015
Amelioration of toxicity in neuronal models of amyotrophic lateral sclerosis by hUPF1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 131 citations in OpenAlex.
- TDP-43 promotes allergen-induced inflammation and influenza A virus replication in airway epithelium.Nature communications · 2026Article
- Isoform-specific steric zippers drive aberrant assembly and mislocalization of shortened TDP-43.Science advances · 2026Article
- RNA-Binding Protein TAF15 Suppresses Toxicity in a Yeast Model of FUS Proteinopathy.Journal of fungi (Basel, Switzerland) · 2026Article
- A next-generation HDAC6 inhibitor for amyotrophic lateral sclerosis and frontotemporal dementia.Brain : a journal of neurology · 2026Article
- Predictive Cellular Signatures from Live Human Motor Neurons Distinguish TDP-43 ALS and Enable ALS Subtype Stratification.bioRxiv : the preprint server for biology · 2026Article
- Toxic mechanisms of amyloid oligomers and therapeutic strategies.Protein science : a publication of the Protein Society · 2026Review
- The function of mRNA quality control in aging and age-related diseases.The Journal of biological chemistry · 2026Review
- Article
- Rsp5/NEDD4 and ESCRT regulate TDP-43 toxicity and turnover via an endolysosomal clearance mechanism.The Journal of cell biology · 2026Article
- Inhibiting Glycogen Synthase Kinase 3 Suppresses TDP-43-Mediated Neurotoxicity in a Caspase-Dependent Manner.Molecular neurobiology · 2026Article
- An autism spectrum disorder mutation in Topoisomerase 3β causes accumulation of covalent mRNA intermediates by disrupting metal binding within the zinc finger domain.Nucleic acids research · 2025Article
- An autism spectrum disorder mutation in Topoisomerase 3β causes accumulation of covalent mRNA intermediates by disrupting metal binding within the zinc finger domain.bioRxiv : the preprint server for biology · 2025Article
- Nemo-like kinase disrupts nuclear import and drives TDP43 mislocalization in ALS.The Journal of clinical investigation · 2025Article
- A toxic gain-of-function variant in MAPK8IP3 provides insights into JIP3 cellular roles.JCI insight · 2025Article
- RNA dysregulation in neurodegenerative diseases.The EMBO journal · 2025Review
- TDP43 autoregulation gives rise to dominant negative isoforms that are tightly controlled by transcriptional and post-translational mechanisms.Cell reports · 2025Article
- Stress granule formation helps to mitigate neurodegeneration.Nucleic acids research · 2024Article
- Aberrant protein aggregation in amyotrophic lateral sclerosis.Journal of neurology · 2024Review
- TDP43 autoregulation gives rise to shortened isoforms that are tightly controlled by both transcriptional and post-translational mechanisms.bioRxiv : the preprint server for biology · 2024Article
- Pathogenic mutations in UBQLN2 exhibit diverse aggregation propensity and neurotoxicity.Scientific reports · 2024Article
31 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
14 authors at 6 institutions in 1 country.
Funding
Abstract
Over 30% of patients with amyotrophic lateral sclerosis (ALS) exhibit cognitive deficits indicative of frontotemporal dementia (FTD), suggesting a common pathogenesis for both diseases. Consistent with this hypothesis, neuronal and glial inclusions rich in TDP43, an essential RNA-binding protein, are found in the majority of those with ALS and FTD, and mutations in TDP43 and a related RNA-binding protein, FUS, cause familial ALS and FTD. TDP43 and FUS affect the splicing of thousands of transcripts, in some cases triggering nonsense-mediated mRNA decay (NMD), a highly conserved RNA degradation pathway. Here, we take advantage of a faithful primary neuronal model of ALS and FTD to investigate and characterize the role of human up-frameshift protein 1 (hUPF1), an RNA helicase and master regulator of NMD, in these disorders. We show that hUPF1 significantly protects mammalian neurons from both TDP43- and FUS-related toxicity. Expression of hUPF2, another essential component of NMD, also improves survival, whereas inhibiting NMD prevents rescue by hUPF1, suggesting that hUPF1 acts through NMD to enhance survival. These studies emphasize the importance of RNA metabolism in ALS and FTD, and identify a uniquely effective therapeutic strategy for these disorders.
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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.