ArticleMolecular biology of the cell2016
The role of gigaxonin in the degradation of the glial-specific intermediate filament protein GFAP.
Article in Molecular biology of the cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Synergistic Effects of Glial Fibrillary Acidic Protein Mutation and Overexpression in the Pathogenesis of Alexander Disease.International journal of molecular sciences · 2026Article
- Deletions in Glial Fibrillary Acidic Protein Leading to Alterations in Intermediate Filament Assembly and Network Formation.International journal of molecular sciences · 2025Article
- Gigaxonin, mutated in Giant Axonal Neuropathy, interacts with TDP-43 and other RNA binding proteins.bioRxiv : the preprint server for biology · 2024Article
- Stability dynamics of neurofilament and GFAP networks and protein fragments.Current opinion in cell biology · 2023Review
- Intermediate filament dysregulation in astrocytes in the human disease model ofMolecular biology of the cell · 2023Article
- Gigaxonin is required for intermediate filament transport.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Intermediate filament dysregulation and astrocytopathy in the human disease model ofbioRxiv : the preprint server for biology · 2023Article
- Symptomatic care of late-onset Alexander disease presenting with area postrema-like syndrome with prednisolone; a case report.BMC pediatrics · 2022Article
- Effects of Alexander disease-associated mutations on the assembly and organization of GFAP intermediate filaments.Molecular biology of the cell · 2022Article
- Proteasome-mediated degradation of keratins 7, 8, 17 and 18 by mutant KLHL24 in a foetal keratinocyte model: Novel insight in congenital skin defects and fragility of epidermolysis bullosa simplex with cardiomyopathy.Human molecular genetics · 2022Article
- Alexander disease: models, mechanisms, and medicine.Current opinion in neurobiology · 2022Review
- The roles of KLHL family members in human cancers.American journal of cancer research · 2022Review
- Case report: Alexander's disease with "head drop" as the main symptom and literature review.Frontiers in neurology · 2022Article
- Human iPSC-Derived Astrocytes: A Powerful Tool to Study Primary Astrocyte Dysfunction in the Pathogenesis of Rare Leukodystrophies.International journal of molecular sciences · 2021Review
- E3 Ubiquitin Ligases in Neurological Diseases: Focus on Gigaxonin and Autophagy.Frontiers in physiology · 2020Review
- Towards genomic database of Alexander disease to identify variations modifying disease phenotype.Scientific reports · 2019Article
- The role of neurofilament aggregation in neurodegeneration: lessons from rare inherited neurological disorders.Molecular neurodegeneration · 2019Review
- Advancing the pathologic phenotype of giant axonal neuropathy: early involvement of the ocular lens.Orphanet journal of rare diseases · 2019Article
- Characterization of a panel of monoclonal antibodies recognizing specific epitopes on GFAP.PloS one · 2017Article
- GFAP at 50.ASN neuroReview
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Alexander disease (AxD) is a primary genetic disorder of astrocytes caused by dominant mutations in the gene encoding the intermediate filament (IF) protein GFAP. This disease is characterized by excessive accumulation of GFAP, known as Rosenthal fibers, within astrocytes. Abnormal GFAP aggregation also occurs in giant axon neuropathy (GAN), which is caused by recessive mutations in the gene encoding gigaxonin. Given that one of the functions of gigaxonin is to facilitate proteasomal degradation of several IF proteins, we sought to determine whether gigaxonin is involved in the degradation of GFAP. Using a lentiviral transduction system, we demonstrated that gigaxonin levels influence the degradation of GFAP in primary astrocytes and in cell lines that express this IF protein. Gigaxonin was similarly involved in the degradation of some but not all AxD-associated GFAP mutants. In addition, gigaxonin directly bound to GFAP, and inhibition of proteasome reversed the clearance of GFAP in cells achieved by overexpressing gigaxonin. These studies identify gigaxonin as an important factor that targets GFAP for degradation through the proteasome pathway. Our findings provide a critical foundation for future studies aimed at reducing or reversing pathological accumulation of GFAP as a potential therapeutic strategy for AxD and related diseases.
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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.