ArticleDisease models & mechanisms2022
Lysosomal alterations and decreased electrophysiological activity in CLN3 disease patient-derived cortical neurons.
Article in Disease models & mechanisms, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 16 citations in OpenAlex.
- Reversible synaptic deficits in early-stage batten disease.Journal of translational medicine · 2026Article
- Modeling CLN3 Batten disease in astrocytes reveals alterations in mitochondria homeostasis, fatty acid metabolism and oxidative stress response.Journal of biomedical science · 2026Article
- Toward Early Diagnosis and Therapeutic Discovery in CLN3 Disease: A Computational Biomarker Discovery Framework.medRxiv : the preprint server for health sciences · 2026Article
- Modelling synaptic dysfunction in childhood dementia using human iPSC-derived cortical networks.Nature communications · 2026Article
- Generation of Donor-Specific iPSC for Modelling Lysosomal Storage Disorders.Methods in molecular biology (Clifton, N.J.) · 2026Article
- A scoping review of stem cell models of leukodystrophies: advances in understanding pathophysiological mechanisms.NPJ genomic medicine · 2025Article
- Discovery of Functionalized 1Journal of medicinal chemistry · 2025Article
- Neuroprotective and Anti-Inflammatory Activity ofMarine drugs · 2025Article
- Role of LIN28B in the Regulation of Ribosomal Biogenesis and Lipid Metabolism in Medulloblastoma Brain Cancer Cells.Proteomes · 2025Article
- Diagnostic analysis of adult neuronal ceroid lipofuscinosis caused by CLN6 gene mutation: a case report.Clinical parkinsonism & related disorders · 2025Article
- Genetic and Cellular Basis of Impaired Phagocytosis and Photoreceptor Degeneration in CLN3 Disease.Investigative ophthalmology & visual science · 2024Article
- How is Excitotoxicity Being Modelled in iPSC-Derived Neurons?Neurotoxicity research · 2024Review
- Targeting autophagy impairment improves the phenotype of a novel CLN8 zebrafish model.Neurobiology of disease · 2024Article
- Supporting the translation of multiscale research in rare disease.Disease models & mechanisms · 2023Article
- Seeing Neurodegeneration in a New Light Using Genetically Encoded Fluorescent Biosensors and iPSCs.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CLN3 disease is a lysosomal storage disorder associated with fatal neurodegeneration that is caused by mutations in CLN3, with most affected individuals carrying at least one allele with a 966 bp deletion. Using CRISPR/Cas9, we corrected the 966 bp deletion mutation in human induced pluripotent stem cells (iPSCs) of a compound heterozygous patient (CLN3 Δ 966 bp and E295K). We differentiated these isogenic iPSCs, and iPSCs from an unrelated healthy control donor, to neurons and identified disease-related changes relating to protein synthesis, trafficking and degradation, and in neuronal activity, which were not apparent in CLN3-corrected or healthy control neurons. CLN3 neurons showed numerous membrane-bound vacuoles containing diverse storage material and hyperglycosylation of the lysosomal LAMP1 protein. Proteomic analysis showed increase in lysosomal-related proteins and many ribosomal subunit proteins in CLN3 neurons, accompanied by downregulation of proteins related to axon guidance and endocytosis. CLN3 neurons also had lower electrophysical activity as recorded using microelectrode arrays. These data implicate inter-related pathways in protein homeostasis and neurite arborization as contributing to CLN3 disease, and which could be potential targets for therapy.
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