ArticleJournal of neuropathology and experimental neurology2010
Alexander disease mutant glial fibrillary acidic protein compromises glutamate transport in astrocytes.
Article in Journal of neuropathology and experimental neurology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 82 citations in OpenAlex.
- Neuroligin-2 is ubiquitinated by Nedd4l to control developmental astrocyte morphogenesis.The Journal of cell biology · 2026Article
- Curing the brain: in search for new astrocyte-specific therapies.Experimental & molecular medicine · 2026Review
- Neuroligin-2 is ubiquitinated by Nedd4l to control developmental astrocyte morphogenesis.bioRxiv : the preprint server for biology · 2025Article
- Electroencephalogram-Guided General Anesthesia in a Pediatric Patient With Alexander's Disease: A Case Report.A&A practice · 2025Article
- Neuroglial Pathophysiology of Leukodystrophies.Advances in neurobiology · 2025Review
- Gene therapy for the leukodystrophies: From preclinical animal studies to clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Preparation and evaluation of controlled released implant containing mesoporous selenium nanoparticles loaded with curcumin in rats with spinal cord injury.Veterinary research forum : an international quarterly journal · 2024Article
- Astrocytes in human central nervous system diseases: a frontier for new therapies.Signal transduction and targeted therapy · 2023Review
- Alexander disease: the road ahead.Neural regeneration research · 2023Review
- Astrocyte contribution to dysfunction, risk and progression in neurodegenerative disorders.Nature reviews. Neuroscience · 2023Review
- Identification of association fibers using ex vivo diffusion tractography in Alexander disease brains.Journal of neuroimaging : official journal of the American Society of Neuroimaging · 2022Article
- The role of astrocyte structural plasticity in regulating neural circuit function and behavior.Glia · 2022Review
- Antisense therapy in a rat model of Alexander disease reverses GFAP pathology, white matter deficits, and motor impairment.Science translational medicine · 2021Article
- The multicellular interplay of microglia in health and disease: lessons from leukodystrophy.Disease models & mechanisms · 2021Review
- Pexidartinib treatment in Alexander disease model mice reduces macrophage numbers and increases glial fibrillary acidic protein levels, yet has minimal impact on other disease phenotypes.Journal of neuroinflammation · 2021Article
- Long-term culturing of porcine nodose ganglia.Journal of neuroscience methods · 2020Article
- Potassium and glutamate transport is impaired in scar-forming tumor-associated astrocytes.Neurochemistry international · 2020Article
- Astrocyte-Oligodendrocyte-Microglia Crosstalk in Astrocytopathies.Frontiers in cellular neuroscience · 2020Review
- Glutamate Carrier Involvement in Mitochondrial Dysfunctioning in the Brain White Matter.Frontiers in molecular biosciences · 2020Article
- Effects of Restraint Water-Immersion Stress-Induced Gastric Mucosal Damage on Astrocytes and Neurons in the Nucleus Raphe Magnus of Rats via the ERK1/2 Signaling Pathway.Neurochemical research · 2019Article
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7 authors at 2 institutions in 1 country.
Funding
Abstract
Alexander disease (AxD) is a leukodystrophy caused by heterozygous mutations in the gene for glial fibrillary acidic protein, an intermediate filament protein expressed by astrocytes. The mutation causes prominent protein aggregates inside astrocytes; there is also loss of myelin and oligodendrocytes and neuronal degeneration. We show that immunohistochemical staining for glutamate transporter 1, the major brain glutamate transporter expressed primarily in astrocytes suggests decreased levels in the hippocampi of infantile AxD patients. A knock-in mouse model of AxD also shows significant reduction of glutamate transporter 1 in the hippocampus. To explore this phenomenon at the cellular level, wild-type and R239C mutant glial fibrillary acidic proteins (the most common mutation) were overexpressed in astrocytes in culture. Western blotting and whole-cell patch clamp recordings demonstrated that the R239C astrocytes exhibited markedly reduced glutamate transporter 1 protein levels; this resulted in attenuated or abolished glutamate-induced inward transporter current. Neurons cocultured with the R239C astrocytes exhibited increased death after glutamate challenge. These results indicate that aberrant astrocytes have decreased glutamate uptake, which may play an important role in the pathogenesis of neuronal and oligodendrocyte injury and death in AxD.
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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.