ArticleMolecular biology of the cell2022
Effects of Alexander disease-associated mutations on the assembly and organization of GFAP intermediate filaments.
Article in Molecular biology of the cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- A systematic review and meta-analysis of GFAP gene variants in Alexander disease.Scientific reports · 2024Pooled it
- Solid state NMR characterization of wild-type and mutant GFAP intermediate filament assemblies.bioRxiv : the preprint server for biology · 2026Article
- Synergistic Effects of Glial Fibrillary Acidic Protein Mutation and Overexpression in the Pathogenesis of Alexander Disease.International journal of molecular sciences · 2026Article
- Alexander disease mutations differentially sensitize glial fibrillary acidic protein (GFAP) to posttranslational modifications and network disruption by oxidants.Redox biology · 2026Article
- Insights into the Structure of Intermediate Filaments.Sub-cellular biochemistry · 2026Review
- Deciphering the Structural Biology of GFAP: Connotations of Its Potency in Presaging the Diagnosis for Traumatic Brain Injury and AD.Neurology international · 2025Review
- Genotype-Phenotype Association for 14Neurology. Genetics · 2025Article
- Deletions in Glial Fibrillary Acidic Protein Leading to Alterations in Intermediate Filament Assembly and Network Formation.International journal of molecular sciences · 2025Article
- Article
- Establishment and Use of Primary Cultured Astrocytes from Alexander Disease Model Mice.International journal of molecular sciences · 2024Article
- Gigaxonin, mutated in Giant Axonal Neuropathy, interacts with TDP-43 and other RNA binding proteins.bioRxiv : the preprint server for biology · 2024Article
- Vimentin filaments integrate low-complexity domains in a complex helical structure.Nature structural & molecular biology · 2024Article
- 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
- Calpain-mediated proteolysis of vimentin filaments is augmented in giant axonal neuropathy fibroblasts exposed to hypotonic stress.Frontiers in cell and developmental biology · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Alexander disease is a primary genetic disorder of astrocytes caused by dominant mutations in the gene encoding glial fibrillary acidic protein (GFAP). How single-amino-acid changes can lead to cytoskeletal catastrophe and brain degeneration remains poorly understood. In this study, we have analyzed 14 missense mutations located in the GFAP rod domain to investigate how these mutations affect in vitro filament assembly. Whereas the internal rod mutants assembled into filaments that were shorter than those of wild type, the rod end mutants formed structures with one or more of several atypical characteristics, including short filament length, irregular width, roughness of filament surface, and filament aggregation. When transduced into primary astrocytes, GFAP mutants with in vitro assembly defects usually formed cytoplasmic aggregates, which were more resistant to biochemical extraction. The resistance of GFAP to solubilization was also observed in brain tissues of patients with Alexander disease, in which a significant proportion of insoluble GFAP were accumulated in Rosenthal fiber fractions. These findings provide clinically relevant evidence that link GFAP assembly defects to disease pathology at the tissue level and suggest that altered filament assembly and properties as a result of GFAP mutation are critical initiating factors for the pathogenesis of Alexander disease.
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Registered trials
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