ArticleScientific reports2019
Increased FUS levels in astrocytes leads to astrocyte and microglia activation and neuronal death.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 46 citations in OpenAlex.
- Targeting astrocyte-mediated neurotoxicity induced by ALS/FTD-associated RNA binding proteins.Cell communication and signaling : CCS · 2026Article
- Retrospective Study of the Physiological and Molecular Features of the S-FUS (1-359) Mouse Transgenic Model with an ALS-like Phenotype: Lifespan, Body Weight Dynamics, Movement Disorders, and Dysregulation of the Dopaminergic System.Journal of molecular neuroscience : MN · 2026Article
- Prematurely Aged Human Microglia Exhibit Impaired Stress Response and Defective Nucleocytoplasmic Shuttling of ALS Associated FUS.Aging cell · 2025Article
- The Roles of hnRNP Family in the Brain and Brain-Related Disorders.Molecular neurobiology · 2024Review
- Cytoplasmic retention of the DNA/RNA-binding protein FUS ameliorates organ fibrosis in mice.The Journal of clinical investigation · 2024Article
- Astrocytes: The Stars in Neurodegeneration?Biomolecules · 2024Review
- Microbiota-gut-brain axis and its therapeutic applications in neurodegenerative diseases.Signal transduction and targeted therapy · 2024Review
- Astrocyte-Neuron Interactions Contributing to Amyotrophic Lateral Sclerosis Progression.Advances in neurobiology · 2024Review
- Neuronal dysfunction caused by FUSR521G promotes ALS-associated phenotypes that are attenuated by NF-κB inhibition.Acta neuropathologica communications · 2023Article
- Lipopolysaccharide triggers exacerbated microglial activation, excessive cytokine release and behavioural disturbances in mice with truncated Fused-in-Sarcoma Protein (FUS).Brain, behavior, & immunity - health · 2023Article
- The Key Role of Astrocytes in Amyotrophic Lateral Sclerosis and Their Commitment to Glutamate Excitotoxicity.International journal of molecular sciences · 2023Review
- FUS-ALS hiPSC-derived astrocytes impair human motor units through both gain-of-toxicity and loss-of-support mechanisms.Molecular neurodegeneration · 2023Article
- Why should we care about astrocytes in a motor neuron disease?Frontiers in molecular medicine · 2023Review
- Is Dutasteride a Therapeutic Alternative for Amyotrophic Lateral Sclerosis?Biomedicines · 2022Review
- Article
- Homozygous ALS-linked FUS P525L mutations cell- autonomously perturb transcriptome profile and chemoreceptor signaling in human iPSC microglia.Stem cell reports · 2022Article
- Frontotemporal Dementia and Glucose Metabolism.Frontiers in neuroscience · 2022Review
- Review
- mInternational journal of molecular sciences · 2021Article
- Wild-Type and Mutant FUS Expression Reduce Proliferation and Neuronal Differentiation Properties of Neural Stem Progenitor Cells.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations of Fused in sarcoma (FUS), a ribonucleoprotein involved in RNA metabolism, have been found associated with both familial and sporadic cases of amyotrophic lateral sclerosis (ALS). Notably, besides mutations in the coding sequence, also mutations into the 3' untranslated region, leading to increased levels of the wild-type protein, have been associated with neuronal death and ALS pathology, in ALS models and patients. The mechanistic link between altered FUS levels and ALS-related neurodegeneration is far to be elucidated, as well as the consequences of elevated FUS levels in the modulation of the inflammatory response sustained by glial cells, a well-recognized player in ALS progression. Here, we studied the effect of wild-type FUS overexpression on the responsiveness of mouse and human neural progenitor-derived astrocytes to a pro-inflammatory stimulus (IL1β) used to mimic an inflammatory environment. We found that astrocytes with increased FUS levels were more sensitive to IL1β, as shown by their enhanced expression of inflammatory genes, compared with control astrocytes. Moreover, astrocytes overexpressing FUS promoted neuronal cell death and pro-inflammatory microglia activation. We conclude that overexpression of wild-type FUS intrinsically affects astrocyte reactivity and drives their properties toward pro-inflammatory and neurotoxic functions, suggesting that a non-cell autonomous mechanism can support neurodegeneration in FUS-mutated animals and patients.
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