ArticleGlia2018
Astrocytes expressing ALS-linked mutant FUS induce motor neuron death through release of tumor necrosis factor-alpha.
Article in Glia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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
74 citing papers in PubMed, 101 citations in OpenAlex.
- Targeting astrocyte-mediated neurotoxicity induced by ALS/FTD-associated RNA binding proteins.Cell communication and signaling : CCS · 2026Article
- Lactate Dehydrogenase Inhibition Reverts the Fatty Acid-Induced Neurotoxic Phenotype of Astrocytes.Glia · 2026Article
- Glial Cells as Key Mediators in the Pathophysiology of Neurodegenerative Diseases.International journal of molecular sciences · 2026Review
- 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
- Traditional Chinese botanical medicines and plant-derived bioactive compounds in amyotrophic lateral sclerosis: mechanistic evidence, translational challenges, and therapeutic opportunities.Frontiers in pharmacology · 2026Review
- The mCells · 2025Review
- Network Dysfunction Precedes Neurodegeneration in a dox-Regulatable TDP-43 Mouse Model of ALS-FTD.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Targeting common disease pathomechanisms to treat amyotrophic lateral sclerosis.Nature reviews. Neurology · 2025Review
- Cell type-specific gene therapy confers protection against motor neuron disease caused by a TFG variant.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Astrocyte-Mediated Neuroinflammation in Neurological Conditions.Biomolecules · 2024Review
- Review
- Review
- Astrocytes: The Stars in Neurodegeneration?Biomolecules · 2024Review
- Crosstalk between Oxidative Stress and Inflammation Caused by Noise and Air Pollution-Implications for Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Astrocyte-Neuron Interactions Contributing to Amyotrophic Lateral Sclerosis Progression.Advances in neurobiology · 2024Review
- The Essential Role of Astrocytes in Neurodegeneration and Neuroprotection.CNS & neurological disorders drug targets · 2024Review
- An Increase in Peroxiredoxin 6 Expression Induces Neurotoxic A1 Astrocytes in the Lumbar Spinal Cord of Amyotrophic Lateral Sclerosis Mice Model.Neurochemical research · 2023Article
- Neuronal dysfunction caused by FUSR521G promotes ALS-associated phenotypes that are attenuated by NF-κB inhibition.Acta neuropathologica communications · 2023Article
- The Key Role of Astrocytes in Amyotrophic Lateral Sclerosis and Their Commitment to Glutamate Excitotoxicity.International journal of molecular sciences · 2023Review
- Review
14 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
5 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in fused in sarcoma (FUS) are linked to amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease affecting both upper and lower motor neurons. While it is established that astrocytes contribute to the death of motor neurons in ALS, the specific contribution of mutant FUS (mutFUS) through astrocytes has not yet been studied. Here, we used primary astrocytes expressing a N-terminally GFP tagged R521G mutant or wild-type FUS (WTFUS) and show that mutFUS-expressing astrocytes undergo astrogliosis, damage co-cultured motor neurons via activation of an inflammatory response and produce conditioned medium (ACM) that is toxic to motor neurons in isolation. Time lapse imaging shows that motor neuron cultures exposed to mutFUS ACM, but not WTFUS ACM, undergo significant cell loss, which is preceded by progressive degeneration of neurites. We found that Tumor Necrosis Factor-Alpha (TNFα) is secreted into ACM of mutFUS-expressing astrocytes. Accordingly, mutFUS astrocyte-mediated motor neuron toxicity is blocked by targeting soluble TNFα with neutralizing antibodies. We also found that mutant astrocytes trigger changes to motor neuron AMPA receptors (AMPAR) that render them susceptible to excitotoxicity and AMPAR-mediated cell death. Our data provide the first evidence of astrocytic involvement in FUS-ALS, identify TNFα as a mediator of this toxicity, and provide several potential therapeutic targets to protect motor neurons in FUS-linked ALS.
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What OpenQuestion holds
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.