ArticleThe Journal of clinical investigation2013
Giant axonal neuropathy-associated gigaxonin mutations impair intermediate filament protein degradation.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 129 citations in OpenAlex.
- The genetic architecture of brainstem structures.Nature communications · 2025Pooled it
- IVNS1ABP mutation drives cellular senescence in newly identified progeroid neuropathy.Nature communications · 2026Article
- PathogenicHuman mutation · 2026Article
- Disease mutation in gigaxonin-E3 ligase recapitulates giant axonal neuropathy in mice.Acta neuropathologica communications · 2025Article
- The Kelch 3 motif on gigaxonin mediates the interaction with NUDCD3 and regulates vimentin filament morphology.European journal of cell biology · 2025Article
- Optogenetic and chemical genetic tools for rapid repositioning of vimentin intermediate filaments.The Journal of cell biology · 2025Article
- Article
- Peripherin, A New Promising Biomarker in Neurological Disorders.The European journal of neuroscience · 2025Review
- Advances in AAV-mediated gene replacement therapy for pediatric monogenic neurological disorders.Molecular therapy. Methods & clinical development · 2024Review
- Gigaxonin, mutated in Giant Axonal Neuropathy, interacts with TDP-43 and other RNA binding proteins.bioRxiv : the preprint server for biology · 2024Article
- Gene therapy for the leukodystrophies: From preclinical animal studies to clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail.Cancer research communications · 2024Article
- Stability dynamics of neurofilament and GFAP networks and protein fragments.Current opinion in cell biology · 2023Review
- The CRL3Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Defining E3 ligase-substrate relationships through multiplex CRISPR screening.Nature cell biology · 2023Article
- Intermediate filament dysregulation in astrocytes in the human disease model ofMolecular biology of the cell · 2023Article
- A multilevel screening pipeline in zebrafish identifies therapeutic drugs for GAN.EMBO molecular medicine · 2023Article
- Axonal Transport Defect in Gigaxonin Deficiency Rescued by Tubastatin A.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- A New Mouse Model of Giant Axonal Neuropathy with Overt Phenotypes and Neurodegeneration Driven by Neurofilament Disorganization.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Gigaxonin is required for intermediate filament transport.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Giant axonal neuropathy (GAN) is an early-onset neurological disorder caused by mutations in the GAN gene (encoding for gigaxonin), which is predicted to be an E3 ligase adaptor. In GAN, aggregates of intermediate filaments (IFs) represent the main pathological feature detected in neurons and other cell types, including patients' dermal fibroblasts. The molecular mechanism by which these mutations cause IFs to aggregate is unknown. Using fibroblasts from patients and normal individuals, as well as Gan-/- mice, we demonstrated that gigaxonin was responsible for the degradation of vimentin IFs. Gigaxonin was similarly involved in the degradation of peripherin and neurofilament IF proteins in neurons. Furthermore, proteasome inhibition by MG-132 reversed the clearance of IF proteins in cells overexpressing gigaxonin, demonstrating the involvement of the proteasomal degradation pathway. Together, these findings identify gigaxonin as a major factor in the degradation of cytoskeletal IFs and provide an explanation for IF aggregate accumulation, the subcellular hallmark of this devastating human disease.
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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.