ArticlePloS one2013
Identification of genetic modifiers of TDP-43 neurotoxicity in Drosophila.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Meta-analysis of Genetic Modifiers Reveals Candidate Dysregulated Pathways in Amyotrophic Lateral Sclerosis.Neuroscience · 2019Pooled it
- Notch-Dependent Expression of theGenes · 2024Article
- MIGGRI: A multi-instance graph neural network model for inferring gene regulatory networks for Drosophila from spatial expression images.PLoS computational biology · 2023Article
- Modelling TDP-43 proteinopathy in Drosophila uncovers shared and neuron-specific targets across ALS and FTD relevant circuits.Acta neuropathologica communications · 2023Article
- A Novel Drosophila-based Drug Repurposing Platform Identified Fingolimod As a Potential Therapeutic for TDP-43 Proteinopathy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Article
- Article
- Integrative genetic analysis illuminates ALS heritability and identifies risk genes.Nature communications · 2023Article
- Unraveling the impact of disrupted nucleocytoplasmic transport systems inFrontiers in cellular neuroscience · 2023Review
- Review
- Amyotrophic Lateral Sclerosis Genes inInternational journal of molecular sciences · 2021Review
- Post-Developmental Roles of Notch Signaling in the Nervous System.Biomolecules · 2020Review
- SMN complex member Gemin3 self-interacts and has a functional relationship with ALS-linked proteins TDP-43, FUS and Sod1.Scientific reports · 2019Article
- A context-based ABC model for literature-based discovery.PloS one · 2019Article
- Notch Signalling in the Hippocampus of Patients With Motor Neuron Disease.Frontiers in neuroscience · 2019Article
- Dynamic duo - FMRP and TDP-43: Regulating common targets, causing different diseases.Brain research · 2018Review
- TDP-43 pathology disrupts nuclear pore complexes and nucleocytoplasmic transport in ALS/FTD.Nature neuroscience · 2018Article
- Mutation-dependent aggregation and toxicity in a Drosophila model for UBQLN2-associated ALS.Human molecular genetics · 2018Article
- TDP-43 in the spectrum of MND-FTLD pathologies.Molecular and cellular neurosciences · 2017Review
- Inside out: the role of nucleocytoplasmic transport in ALS and FTLD.Acta neuropathologica · 2016Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Cytosolic aggregation of the nuclear RNA-binding protein TDP-43 is a histopathologic signature of degenerating neurons in amyotrophic lateral sclerosis (ALS), and mutations in the TARDBP gene encoding TDP-43 cause dominantly inherited forms of this condition. To understand the relationship between TDP-43 misregulation and neurotoxicity, we and others have used Drosophila as a model system, in which overexpression of either wild-type TDP-43 or its ALS-associated mutants in neurons is sufficient to induce neurotoxicity, paralysis, and early death. Using microarrays, we have examined gene expression patterns that accompany TDP-43-induced neurotoxicity in the fly system. Constitutive expression of TDP-43 in the Drosophila compound eye elicited widespread gene expression changes, with strong upregulation of cell cycle regulatory genes and genes functioning in the Notch intercellular communication pathway. Inducible expression of TDP-43 specifically in neurons elicited significant expression differences in a more restricted set of genes. Genes that were upregulated in both paradigms included SpindleB and the Notch target Hey, which appeared to be a direct TDP-43 target. Mutations that diminished activity of Notch or disrupted the function of downstream Notch target genes extended the lifespan of TDP-43 transgenic flies, suggesting that Notch activation was deleterious in this model. Finally, we showed that mutation of the nucleoporin Nup50 increased the lifespan of TDP-43 transgenic flies, suggesting that nuclear events contribute to TDP-43-dependent neurotoxicity. The combined findings identified pathways whose deregulation might contribute to TDP-43-induced neurotoxicity in Drosophila.
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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.