ArticleCell reports2018
Mutations in GFAP Disrupt the Distribution and Function of Organelles in Human Astrocytes.
Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 69 citations in OpenAlex.
- GFAP degradation in TBI: linking novel modified products to astrocyte pathology and patient outcome.Acta neuropathologica communications · 2026Article
- CK2 inhibition suppresses glial inflammation in models of neuroinflammation and neurodegeneration.Nature communications · 2026Article
- Cellular Characterization Using Microwave-Assisted Immunocytochemistry, A Time-Efficient Alternative to Traditional Immunocytochemistry.Current protocols · 2026Article
- Heterogeneity of astrocyte density, morphology and connexins in the mouse hippocampus.Frontiers in neuroanatomy · 2026Article
- The intermediate filament protein GFAP regulates mitochondrial fission in astrocytes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A scoping review of stem cell models of leukodystrophies: advances in understanding pathophysiological mechanisms.NPJ genomic medicine · 2025Article
- Article
- Morphological Characteristics and Extracellular Matrix Abnormalities in Astrocytes Derived From iPSCs of Children With Alexander Disease.CNS neuroscience & therapeutics · 2025Article
- Neuroglial Pathophysiology of Leukodystrophies.Advances in neurobiology · 2025Review
- Electroencephalogram-Guided General Anesthesia in a Pediatric Patient With Alexander's Disease: A Case Report.A&A practice · 2025Article
- Article
- Establishment and Use of Primary Cultured Astrocytes from Alexander Disease Model Mice.International journal of molecular sciences · 2024Article
- Human iN neuronal model of schizophrenia displays dysregulation of chromogranin B and related neuropeptide transmitter signatures.Molecular psychiatry · 2024Article
- Induced pluripotent stem cell-based assays recapture multiple properties of human astrocytes.Journal of cellular and molecular medicine · 2024Article
- 3D bioprinting of human neural tissues with functional connectivity.Cell stem cell · 2024Article
- Regulation of adult neurogenesis: the crucial role of astrocytic mitochondria.Frontiers in molecular neuroscience · 2024Review
- Stability dynamics of neurofilament and GFAP networks and protein fragments.Current opinion in cell biology · 2023Review
- Alexander disease: the road ahead.Neural regeneration research · 2023Review
- A defined roadmap of radial glia and astrocyte differentiation from human pluripotent stem cells.Stem cell reports · 2023Article
- High-fat diet induces depression-like phenotype via astrocyte-mediated hyperactivation of ventral hippocampal glutamatergic afferents to the nucleus accumbens.Molecular psychiatry · 2022Article
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
How mutations in glial fibrillary acidic protein (GFAP) cause Alexander disease (AxD) remains elusive. We generated iPSCs from two AxD patients and corrected the GFAP mutations to examine the effects of mutant GFAP on human astrocytes. AxD astrocytes displayed GFAP aggregates, recapitulating the pathological hallmark of AxD. RNA sequencing implicated the endoplasmic reticulum, vesicle regulation, and cellular metabolism. Corroborating this analysis, we observed enlarged and heterogeneous morphology coupled with perinuclear localization of endoplasmic reticulum and lysosomes in AxD astrocytes. Functionally, AxD astrocytes showed impaired extracellular ATP release, which is responsible for attenuated calcium wave propagation. These results reveal that AxD-causing mutations in GFAP disrupt intracellular vesicle regulation and impair astrocyte secretion, resulting in astrocyte dysfunction and AxD pathogenesis.
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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.