ArticleProceedings of the National Academy of Sciences of the United States of America2005
Insights into Lafora disease: malin is an E3 ubiquitin ligase that ubiquitinates and promotes the degradation of laforin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 1 of them a synthesis that pooled it.
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Who cites it
125 citing papers in PubMed, 1 synthesis or guideline pooled it, 239 citations in OpenAlex.
- Prognostic value of pathogenic variants in Lafora Disease: systematic review and meta-analysis of patient-level data.Orphanet journal of rare diseases · 2023Pooled it
- Genetic and epigenetic underpinnings of biological aging: a multi-omics study integrating Mendelian randomization, spatial transcriptomics, and drug target discovery.Clinical epigenetics · 2026Article
- Article
- Lafora disease gene therapy: EPM2A but not EPM2B overexpression results in Lafora body formation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Adeno-Associated Virus-Based Gene Therapy for Lafora Disease inInternational journal of molecular sciences · 2025Article
- Advances in gene therapy for Lafora disease: Intravenous recombinant adeno-associated virus-mediated delivery of EPM2A and EPM2B genes.Clinical and translational medicine · 2025Article
- The 9th annual Lafora science symposium: a rare epilepsy community makes progress towards clinical readiness.Epilepsy & behavior : E&B · 2025Article
- Discovery and Evaluation of Active Site-Directed, Potent, and Selective Sulfophenyl Acetic Amide-Based Inhibitors for the Laforin Phosphatase.Journal of medicinal chemistry · 2025Article
- Neuromuscular junction dysfunction in Lafora disease.Disease models & mechanisms · 2024Article
- Gene therapy for Lafora disease in the Epm2aMolecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Predictive modeling for ubiquitin proteins through advanced machine learning technique.Heliyon · 2024Article
- The multifaceted roles of the brain glycogen.Journal of neurochemistry · 2024Review
- Myofiber-type-dependent 'boulder' or 'multitudinous pebble' formations across distinct amylopectinoses.Acta neuropathologica · 2024Article
- Effect of intracerebroventricular administration of alglucosidase alfa in two mouse models of Lafora disease: Relevance for clinical practice.Epilepsy research · 2024Article
- Lafora progressive myoclonus epilepsy: Disease mechanism and therapeutic attempts.Journal of biosciences · 2024Review
- Article
- Lafora Disease: A Case Report and Evolving Treatment Advancements.Brain sciences · 2023Article
- MRI characteristics due to gene mutations in a Chinese pedigree with Lafora disease.Molecular genetics & genomic medicine · 2023Article
- Gys1 Antisense Therapy Prevents Disease-Driving Aggregates and Epileptiform Discharges in a Lafora Disease Mouse Model.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Spatial metabolomics reveals glycogen as an actionable target for pulmonary fibrosis.Nature communications · 2023Article
65 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Lafora disease (LD) is a fatal form of progressive myoclonus epilepsy caused by recessive mutations in either a gene encoding a dual-specificity phosphatase, known as laforin, or a recently identified gene encoding the protein known as malin. Here, we demonstrate that malin is a single subunit E3 ubiquitin (Ub) ligase and that its RING domain is necessary and sufficient to mediate ubiquitination. Additionally, malin interacts with and polyubiquitinates laforin, leading to its degradation. Missense mutations in malin that are present in LD patients abolish its ability to polyubiquitinate and signal the degradation of laforin. Our results demonstrate that laforin is a physiologic substrate of malin, and we propose possible models to explain how recessive mutations in either malin or laforin result in LD. Furthermore, these data distinguish malin as an E3 Ub ligase whose activity is necessary to prevent a neurodegenerative disease that involves formation of nonproteinacious inclusion bodies.
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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 OpenQuestion graph.