ArticleStem cell reports2021
Astrocytic reactivity triggered by defective autophagy and metabolic failure causes neurotoxicity in frontotemporal dementia type 3.
Article in Stem cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- The rise of astrocytes: are they guardians or troublemakers of the brain disorder?Experimental & molecular medicine · 2026Review
- Cytoskeleton-mediated autophagy regulation in neuroimmune contexts: molecular mechanisms and functional perspectives.Frontiers in immunology · 2026Review
- Role of astrocytes in the pathogenesis of perinatal brain injury.Molecular medicine (Cambridge, Mass.) · 2025Review
- Autophagy and Cellular Senescence in Alzheimer's Disease: Key Drivers of Neurodegeneration.CNS neuroscience & therapeutics · 2025Review
- Autophagy in alzheimer disease pathogenesis and its therapeutic values.Autophagy reports · 2025Review
- Targeting autophagy in astrocytes: a potential for neurodegenerative disease intervention.Frontiers in cellular neuroscience · 2025Review
- Delivery of TGFβ3 from Magnetically Responsive Coaxial Fibers Reduces Spinal Cord Astrocyte Reactivity In Vitro.Advanced biology · 2024Article
- Comprehensive Overview of Alzheimer's Disease: Etiological Insights and Degradation Strategies.International journal of molecular sciences · 2024Review
- Autophagy in neural stem cells and glia for brain health and diseases.Neural regeneration research · 2024Review
- Astrocytes in selective vulnerability to neurodegenerative disease.Trends in neurosciences · 2024Review
- Astrocytes: The Stars in Neurodegeneration?Biomolecules · 2024Review
- Generation of Human Induced Pluripotent Stem Cell (hiPSC)-Derived Astrocytes for Amyotrophic Lateral Sclerosis and Other Neurodegenerative Disease Studies.Bio-protocol · 2024Article
- BNIP3 as a new tool to promote healthy brain aging.Aging cell · 2024Review
- In vitro assessment of protamine toxicity with neural cells, its therapeutic potential to counter chondroitin sulfate mediated neuron inhibition, and its effects on reactive astrocytes.Advanced therapeutics · 2024Article
- The interaction of lipocalin-2 and astrocytes in neuroinflammation: mechanisms and therapeutic application.Frontiers in immunology · 2024Review
- Efficient derivation of functional astrocytes from human induced pluripotent stem cells (hiPSCs).PloS one · 2024Article
- Cell-specific alterations in autophagy-lysosomal activity near the chronically implanted microelectrodes.Biomaterials · 2023Article
- Cell-Type-Specific Mitochondrial Quality Control in the Brain: A Plausible Mechanism of Neurodegeneration.International journal of molecular sciences · 2023Review
- Astrocytes: Dissecting Their Diverse Roles in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.Cells · 2023Review
- FUS-ALS hiPSC-derived astrocytes impair human motor units through both gain-of-toxicity and loss-of-support mechanisms.Molecular neurodegeneration · 2023Article
Corrections and comments
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Authors and funding
25 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Frontotemporal dementia type 3 (FTD3), caused by a point mutation in the charged multivesicular body protein 2B (CHMP2B), affects mitochondrial ultrastructure and the endolysosomal pathway in neurons. To dissect the astrocyte-specific impact of mutant CHMP2B expression, we generated astrocytes from human induced pluripotent stem cells (hiPSCs) and confirmed our findings in CHMP2B mutant mice. Our data provide mechanistic insights into how defective autophagy causes perturbed mitochondrial dynamics with impaired glycolysis, increased reactive oxygen species, and elongated mitochondrial morphology, indicating increased mitochondrial fusion in FTD3 astrocytes. This shift in astrocyte homeostasis triggers a reactive astrocyte phenotype and increased release of toxic cytokines, which accumulate in nuclear factor kappa b (NF-κB) pathway activation with increased production of CHF, LCN2, and C3 causing neurodegeneration.
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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.