ArticleHuman molecular genetics2018
FUS-induced neurotoxicity in Drosophila is prevented by downregulating nucleocytoplasmic transport proteins.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Impaired nucleocytoplasmic transport in SOD1-mediated ALS.Molecular neurodegeneration · 2026Article
- Heterogeneous Nuclear Ribonucleoprotein A1 Knockdown Alters Constituents of Nucleocytoplasmic Transport.Brain sciences · 2024Article
- Targeting RACK1 to alleviate TDP-43 and FUS proteinopathy-mediated suppression of protein translation and neurodegeneration.Acta neuropathologica communications · 2023Article
- Pathological insights from amyotrophic lateral sclerosis animal models: comparisons, limitations, and challenges.Translational neurodegeneration · 2023Review
- Unraveling the impact of disrupted nucleocytoplasmic transport systems inFrontiers in cellular neuroscience · 2023Review
- Review
- MiR-483-3p improves learning and memory abilities via XPO1 in Alzheimer's disease.Brain and behavior · 2022Article
- The Role of Nucleocytoplasmic Transport Defects in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2021Review
- All Roads Lead to Rome: Different Molecular Players Converge to Common Toxic Pathways in Neurodegeneration.Cells · 2021Review
- Fly for ALS: Drosophila modeling on the route to amyotrophic lateral sclerosis modifiers.Cellular and molecular life sciences : CMLS · 2021Review
- Interactions between ALS-linked FUS and nucleoporins are associated with defects in the nucleocytoplasmic transport pathway.Nature neuroscience · 2021Article
- The phase separation-dependent FUS interactome reveals nuclear and cytoplasmic function of liquid-liquid phase separation.Nucleic acids research · 2021Article
- Nucleocytoplasmic Transport: Regulatory Mechanisms and the Implications in Neurodegeneration.International journal of molecular sciences · 2021Review
- Where and Why Modeling Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2021Review
- Role and therapeutic potential of liquid-liquid phase separation in amyotrophic lateral sclerosis.Journal of molecular cell biology · 2021Review
- Amyotrophic Lateral Sclerosis Genes inInternational journal of molecular sciences · 2021Review
- Trends in Understanding the Pathological Roles of TDP-43 and FUS Proteins.Advances in experimental medicine and biology · 2021Article
- Potential Therapeutic Role of HDAC Inhibitors in FUS-ALS.Frontiers in molecular neuroscience · 2021Review
- Stress granule subtypes: an emerging link to neurodegeneration.Cellular and molecular life sciences : CMLS · 2020Review
- Nucleo-cytoplasmic transport defects and protein aggregates in neurodegeneration.Translational neurodegeneration · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases characterized by the progressive loss of specific groups of neurons. Due to clinical, genetic and pathological overlap, both diseases are considered as the extremes of one disease spectrum and in a number of ALS and FTD patients, fused in sarcoma (FUS) aggregates are present. Even in families with a monogenetic disease cause, a striking variability is observed in disease presentation. This suggests the presence of important modifying genes. The identification of disease-modifying genes will contribute to defining clear therapeutic targets and to understanding the pathways involved in motor neuron death. In this study, we established a novel in vivo screening platform in which new modifying genes of FUS toxicity can be identified. Expression of human FUS induced the selective apoptosis of crustacean cardioactive peptide (CCAP) neurons from the ventral nerve cord of fruit flies. No defects in the development of these neurons were observed nor were the regulatory CCAP neurons from the brain affected. We used the number of CCAP neurons from the ventral nerve cord as an in vivo read-out for FUS toxicity in neurons. Via a targeted screen, we discovered a potent modifying role of proteins involved in nucleocytoplasmic transport. Downregulation of Nucleoporin 154 and Exportin1 (XPO1) prevented FUS-induced neurotoxicity. Moreover, we show that XPO1 interacted with FUS. Silencing XPO1 significantly reduced the propensity of FUS to form inclusions upon stress. Taken together, our findings point to an important role of nucleocytoplasmic transport proteins in FUS-induced ALS/FTD.
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