ArticleThe Journal of clinical investigation2011
The ALS-associated proteins FUS and TDP-43 function together to affect Drosophila locomotion and life span.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 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
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Who cites it
110 citing papers in PubMed, 1 synthesis or guideline pooled it, 171 citations in OpenAlex.
- Meta-analysis of Genetic Modifiers Reveals Candidate Dysregulated Pathways in Amyotrophic Lateral Sclerosis.Neuroscience · 2019Pooled it
- RNA-Binding Protein TAF15 Suppresses Toxicity in a Yeast Model of FUS Proteinopathy.Journal of fungi (Basel, Switzerland) · 2026Article
- Granules Gone Rogue: Nuclear and Cytoplasmic Ribonucleoprotein Structures in Amyotrophic Lateral Sclerosis-Fused in Sarcoma (ALS-FUS) Pathology.Molecular neurobiology · 2026Review
- From development to disease: the neuronal role of hnRNPs through the lens ofFrontiers in cell and developmental biology · 2026Review
- TDP-43 as a potential retinal biomarker for neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- Dysregulated FOXO1 activity drives skeletal muscle intrinsic dysfunction in amyotrophic lateral sclerosis.Acta neuropathologica · 2024Article
- Understanding Amyotrophic Lateral Sclerosis: Pathophysiology, Diagnosis, and Therapeutic Advances.International journal of molecular sciences · 2024Review
- Hyperhidrosis as the initial symptom in FUS mutation-associated amyotrophic lateral sclerosis: a case report and comprehensive literature review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Review
- Analysis of asymptomatic Drosophila models for ALS and SMA reveals convergent impact on functional protein complexes linked to neuro-muscular degeneration.BMC genomics · 2023Article
- Pathological insights from amyotrophic lateral sclerosis animal models: comparisons, limitations, and challenges.Translational neurodegeneration · 2023Review
- FUS regulates RAN translation through modulating the G-quadruplex structure of GGGGCC repeat RNA ineLife · 2023Article
- A nerve-wracking buzz: lessons fromFrontiers in aging neuroscience · 2023Review
- TDP-43 dysregulation and neuromuscular junction disruption in amyotrophic lateral sclerosis.Translational neurodegeneration · 2022Review
- Review
- Molecular and Developmental Signatures of Genital Size Macro-Evolution in Bugs.Molecular biology and evolution · 2022Article
- Mechanistic Insights of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis: An Update on a Lasting Relationship.Metabolites · 2022Review
- Inter-Species Rescue of Mutant Phenotype-The Standard for Genetic Analysis of Human Genetic Disorders inInternational journal of molecular sciences · 2022Review
- Nearly 30 Years of Animal Models to Study Amyotrophic Lateral Sclerosis: A Historical Overview and Future Perspectives.International journal of molecular sciences · 2021Review
- Fly for ALS: Drosophila modeling on the route to amyotrophic lateral sclerosis modifiers.Cellular and molecular life sciences : CMLS · 2021Review
- Article
50 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The fatal adult motor neuron disease amyotrophic lateral sclerosis (ALS) shares some clinical and pathological overlap with frontotemporal dementia (FTD), an early-onset neurodegenerative disorder. The RNA/DNA-binding proteins fused in sarcoma (FUS; also known as TLS) and TAR DNA binding protein-43 (TDP-43) have recently been shown to be genetically and pathologically associated with familial forms of ALS and FTD. It is currently unknown whether perturbation of these proteins results in disease through mechanisms that are independent of normal protein function or via the pathophysiological disruption of molecular processes in which they are both critical. Here, we report that Drosophila mutants in which the homolog of FUS is disrupted exhibit decreased adult viability, diminished locomotor speed, and reduced life span compared with controls. These phenotypes were fully rescued by wild-type human FUS, but not ALS-associated mutant FUS proteins. A mutant of the Drosophila homolog of TDP-43 had similar, but more severe, deficits. Through cross-rescue analysis, we demonstrated that FUS acted together with and downstream of TDP-43 in a common genetic pathway in neurons. Furthermore, we found that these proteins associated with each other in an RNA-dependent complex. Our results establish that FUS and TDP-43 function together in vivo and suggest that molecular pathways requiring the combined activities of both of these proteins may be disrupted in ALS and FTD.
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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.