ArticleActa neuropathologica communications2017
The origin of Rosenthal fibers and their contributions to astrocyte pathology in Alexander disease.
Article in Acta neuropathologica communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- A systematic review and meta-analysis of GFAP gene variants in Alexander disease.Scientific reports · 2024Pooled it
- Progressive gait and motor deficits in a rat model of Alexander disease.Behavioural brain research · 2026Article
- Synergistic Effects of Glial Fibrillary Acidic Protein Mutation and Overexpression in the Pathogenesis of Alexander Disease.International journal of molecular sciences · 2026Article
- Adult spinal cord diffuse midline gliomas with piloid features have a better prognosis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- A scoping review of stem cell models of leukodystrophies: advances in understanding pathophysiological mechanisms.NPJ genomic medicine · 2025Article
- Alexander's Disease: Potential Drug Targets and Future Directions.Molecular neurobiology · 2025Review
- Article
- PepTune:ArXiv · 2025Article
- Article
- Development of perivascular astrocyte processes.Frontiers in neuroscience · 2025Review
- Morphological Characteristics and Extracellular Matrix Abnormalities in Astrocytes Derived From iPSCs of Children With Alexander Disease.CNS neuroscience & therapeutics · 2025Article
- Establishment and Use of Primary Cultured Astrocytes from Alexander Disease Model Mice.International journal of molecular sciences · 2024Article
- Therapeutic targeting of differentiation-state dependent metabolic vulnerabilities in diffuse midline glioma.Nature communications · 2024Article
- Sexual size dimorphism in mammals is associated with changes in the size of gene families related to brain development.Nature communications · 2024Article
- Gene therapy for the leukodystrophies: From preclinical animal studies to clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- hPSC-Derived Astrocytes at the Forefront of Translational Applications in Neurological Disorders.Cells · 2024Review
- Intermediate filament dysregulation in astrocytes in the human disease model ofMolecular biology of the cell · 2023Article
- Intermediate filament dysregulation and astrocytopathy in the human disease model ofbioRxiv : the preprint server for biology · 2023Article
- 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
- Effects of Alexander disease-associated mutations on the assembly and organization of GFAP intermediate filaments.Molecular biology of the cell · 2022Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Rosenthal fibers (RFs) are cytoplasmic, proteinaceous aggregates. They are the pathognomonic feature of the astrocyte pathology in Alexander Disease (AxD), a neurodegenerative disorder caused by heterozygous mutations in the GFAP gene, encoding glial fibrillary acidic protein (GFAP). Although RFs have been known for many years their origin and significance remain elusive issues. We have used mouse models of AxD based on the overexpression of human GFAP (transgenic, TG) and a point mutation in mouse GFAP (knock-in, KI) to examine the formation of RFs and to find astrocyte changes that correlate with the appearance of RFs. We found RFs of various sizes and shapes. The smallest ones appear as granular depositions on intermediate filaments. These contain GFAP and the small heat shock protein, alphaB-crystallin. Their aggregation appears to give rise to large RFs. The appearance of new RFs and the growth of previously formed RFs occur over time. We determined that DAPI is a reliable marker of RFs and in parallel with Fluoro-Jade B (FJB) staining defined a high variability in the appearance of RFs, even in neighboring astrocytes. Although many astrocytes in AxD with increased levels of GFAP and with or without RFs change their phenotype, only some cells with large numbers of RFs show a profound reconstruction of cellular processes, with a loss of fine distal processes and the appearance of large, lobulated nuclei, likely due to arrested mitosis. We conclude that 1) RFs appear to originate as small, osmiophilic masses containing both GFAP and alphaB-crystallin deposited on bundles of intermediate filaments. 2) RFs continue to form within AxD astrocytes over time. 3) DAPI is a reliable marker for RFs and can be used with immunolabeling. 4) RFs appear to interfere with the successful completion of astrocyte mitosis and cell division.
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