ArticleHuman molecular genetics2015
Intermediate filament protein accumulation in motor neurons derived from giant axonal neuropathy iPSCs rescued by restoration of gigaxonin.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 41 citations in OpenAlex.
- A scoping review of stem cell models of leukodystrophies: advances in understanding pathophysiological mechanisms.NPJ genomic medicine · 2025Article
- Advances in Induced Pluripotent Stem Cell Reprogramming and Its Application in Amyotrophic Lateral Sclerosis: A Review.FASEB bioAdvances · 2025Review
- Charcot-Marie-Tooth-like presentation in giant axonal neuropathy: clinical variability and prevalence in a large Japanese case series.Journal of neurology · 2025Article
- 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
- KIF1A, R1457Q, and P1688L Mutations Induce Protein Abnormal Aggregation and Autophagy Impairment in iPSC-Derived Motor Neurons.Biomedicines · 2024Article
- Gene therapy for the leukodystrophies: From preclinical animal studies to clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Neurofilament Biophysics: From Structure to Biomechanics.Molecular biology of the cell · 2024Review
- The CRL3Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Intermediate filament dysregulation in astrocytes in the human disease model ofMolecular biology of the cell · 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
- Intermediate filament dysregulation and astrocytopathy in the human disease model ofbioRxiv : the preprint server for biology · 2023Article
- Genetic Approaches for the Treatment of Giant Axonal Neuropathy.Journal of personalized medicine · 2022Review
- Human iPSC-Derived Astrocytes: A Powerful Tool to Study Primary Astrocyte Dysfunction in the Pathogenesis of Rare Leukodystrophies.International journal of molecular sciences · 2021Review
- Giant axonal neuropathy: cross-sectional analysis of a large natural history cohort.Brain : a journal of neurology · 2021Article
- Neurofilaments: neurobiological foundations for biomarker applications.Brain : a journal of neurology · 2020Review
- Gigaxonin glycosylation regulates intermediate filament turnover and may impact giant axonal neuropathy etiology or treatmentJCI insight · 2020Article
- E3 Ubiquitin Ligases in Neurological Diseases: Focus on Gigaxonin and Autophagy.Frontiers in physiology · 2020Review
- Giant axonal neuropathy: a multicenter retrospective study with genotypic spectrum expansion.Neurogenetics · 2020Observational
- Sonic Hedgehog repression underlies gigaxonin mutation-induced motor deficits in giant axonal neuropathy.The Journal of clinical investigation · 2019Article
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 4 countries.
Funding
Abstract
Giant axonal neuropathy (GAN) is a progressive neurodegenerative disease caused by autosomal recessive mutations in the GAN gene resulting in a loss of a ubiquitously expressed protein, gigaxonin. Gene replacement therapy is a promising strategy for treatment of the disease; however, the effectiveness and safety of gigaxonin reintroduction have not been tested in human GAN nerve cells. Here we report the derivation of induced pluripotent stem cells (iPSCs) from three GAN patients with different GAN mutations. Motor neurons differentiated from GAN iPSCs exhibit accumulation of neurofilament (NF-L) and peripherin (PRPH) protein and formation of PRPH aggregates, the key pathological phenotypes observed in patients. Introduction of gigaxonin either using a lentiviral vector or as a stable transgene resulted in normalization of NEFL and PRPH levels in GAN neurons and disappearance of PRPH aggregates. Importantly, overexpression of gigaxonin had no adverse effect on survival of GAN neurons, supporting the feasibility of gene replacement therapy. Our findings demonstrate that GAN iPSCs provide a novel model for studying human GAN neuropathologies and for the development and testing of new therapies in relevant cell types.
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