ArticleFrontiers in cellular neuroscience2020
Human Motor Neurons With SOD1-G93A Mutation Generated From CRISPR/Cas9 Gene-Edited iPSCs Develop Pathological Features of Amyotrophic Lateral Sclerosis.
Article in Frontiers in cellular neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 56 citations in OpenAlex.
- Human iPSC-derived motor neurons as a platform for elucidating TDP-43-related amyotrophic lateral sclerosis pathogenesis: a mini review.Frontiers in molecular neuroscience · 2026Review
- Modeling ALS in a dish: how organoids are transforming research.Frontiers in medicine · 2026Review
- CRISPR/Cas9 a genomic engineering technology for treatment in ALS mouse models.Regenerative therapy · 2025Review
- Cutting-edge treatments in amyotrophic lateral sclerosis: the role of molecular pathogenesis in targeted therapies.Stem cell research & therapy · 2025Review
- Applications of CRISPR-Cas9 in mitigating cellular senescence and age-related disease progression.Clinical and experimental medicine · 2025Review
- Article
- Axonopathy Underlying Amyotrophic Lateral Sclerosis: Unraveling Complex Pathways and Therapeutic Insights.Neuroscience bulletin · 2024Review
- Polyethyleneimine facilitates the growth and electrophysiological characterization of iPSC-derived motor neurons.Scientific reports · 2024Article
- How is Excitotoxicity Being Modelled in iPSC-Derived Neurons?Neurotoxicity research · 2024Review
- In vivo and ex vivo gene therapy for neurodegenerative diseases: a promise for disease modification.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Nuclear Localization of Human SOD1 in Motor Neurons in Mouse Model and Patient Amyotrophic Lateral Sclerosis: Possible Links to Cholinergic Phenotype, NADPH Oxidase, Oxidative Stress, and DNA Damage.International journal of molecular sciences · 2024Article
- Advances in Exosome-Based Therapies for the Repair of Peripheral Nerve Injuries.Neurochemical research · 2024Review
- Homozygous ALS-linked mutations in TARDBP/TDP-43 lead to hypoactivity and synaptic abnormalities in human iPSC-derived motor neurons.iScience · 2024Article
- Mitochondria: A Promising Convergent Target for the Treatment of Amyotrophic Lateral Sclerosis.Cells · 2024Review
- Genetically modified mice as a tool for the study of human diseases.Molecular biology reports · 2024Review
- Using Human-Induced Pluripotent Stem Cell Derived Neurons on Microelectrode Arrays to Model Neurological Disease: A Review.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Specific vulnerability of iPSC-derived motor neurons with TDP-43 gene mutation to oxidative stress.Molecular brain · 2023Article
- Enhanced axonal regeneration of ALS patient iPSC-derived motor neurons harboring SOD1Scientific reports · 2023Article
- Advancement in CRISPR/Cas9 Technology to Better Understand and Treat Neurological Disorders.Cellular and molecular neurobiology · 2023Review
- An Optimized Workflow to Generate and Characterize iPSC-Derived Motor Neuron (MN) Spheroids.Cells · 2023Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by gradual degeneration and elimination of motor neurons (MNs) in the motor cortex, brainstem, and spinal cord. Some familial forms of ALS are caused by genetic mutations in superoxide dismutase 1 (SOD1) but the mechanisms driving MN disease are unclear. Identifying the naturally occurring pathology and understanding how this mutant SOD1 can affect MNs in translationally meaningful ways in a valid and reliable human cell model remains to be established. Here, using CRISPR/Cas9 genome editing system and human induced pluripotent stem cells (iPSCs), we generated highly pure, iPSC-derived MNs with a SOD1-G93A missense mutation. With the wild-type cell line serving as an isogenic control and MNs from a patient-derived iPSC line with an SOD1-A4V mutation as a comparator, we identified pathological phenotypes relevant to ALS. The mutant MNs accumulated misfolded and aggregated forms of SOD1 in cell bodies and processes, including axons. They also developed distinctive axonal pathologies. Mutants had axonal swellings with shorter axon length and less numbers of branch points. Moreover, structural and molecular abnormalities in presynaptic and postsynaptic size and density were found in the mutants. Finally, functional studies with microelectrode array demonstrated that the individual mutant MNs exhibited decreased number of spikes and diminished network bursting, but increased burst duration. Taken together, we identified spontaneous disease phenotypes relevant to ALS in mutant SOD1 MNs from genome-edited and patient-derived iPSCs. Our findings demonstrate that SOD1 mutations in human MNs cause cell-autonomous proteinopathy, axonopathy, synaptic pathology, and aberrant neurotransmission.
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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 Socratic graph.