ArticleMolecular neurobiology2016
Pharmacological Interventions to Ameliorate Neuropathological Symptoms in a Mouse Model of Lafora Disease.
Article in Molecular neurobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Glucose metabolism impairment as a hallmark of progressive myoclonus epilepsies: a focus on neuronal ceroid lipofuscinoses.Frontiers in cellular neuroscience · 2024Pooled it
- 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
- 4-Phenylbutyric Acid Improves Gait Ability of UBAP1-Related Spastic Paraplegia Mouse Model: Therapeutic Potential for SPG80.International journal of molecular sciences · 2025Article
- Epilepsy and autophagy modulators: a therapeutic split.Autophagy · 2025Review
- Neurological glycogen storage diseases and emerging therapeutics.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Gene therapy for Lafora disease in the Epm2aMolecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Beneficial Effect of Fingolimod in a Lafora Disease Mouse Model by Preventing Reactive Astrogliosis-Derived Neuroinflammation and Brain Infiltration of T-lymphocytes.Molecular neurobiology · 2024Article
- Neuroinflammation and Epilepsy: From Pathophysiology to Therapies Based on Repurposing Drugs.International journal of molecular sciences · 2024Review
- Progressive Myoclonus Epilepsy: A Scoping Review of Diagnostic, Phenotypic and Therapeutic Advances.Genes · 2024Article
- Lafora progressive myoclonus epilepsy: Disease mechanism and therapeutic attempts.Journal of biosciences · 2024Review
- Lafora Disease: A Case Report and Evolving Treatment Advancements.Brain sciences · 2023Article
- New insights on the potential anti-epileptic effect of metformin: Mechanistic pathway.Journal of cellular and molecular medicine · 2023Review
- Autophagy and autophagy signaling in Epilepsy: possible role of autophagy activator.Molecular medicine (Cambridge, Mass.) · 2023Review
- MRI characteristics due to gene mutations in a Chinese pedigree with Lafora disease.Molecular genetics & genomic medicine · 2023Article
- ILAE Genetics Literacy series: Progressive myoclonus epilepsies.Epileptic disorders : international epilepsy journal with videotape · 2023Review
- Deciphering the Polyglucosan Accumulation Present in Lafora Disease Using an Astrocytic Cellular Model.International journal of molecular sciences · 2023Article
- Age-Related microRNA Overexpression in Lafora Disease Male Mice Provides Links between Neuroinflammation and Oxidative Stress.International journal of molecular sciences · 2023Article
- TNF and IL6/Jak2 signaling pathways are the main contributors of the glia-derived neuroinflammation present in Lafora disease, a fatal form of progressive myoclonus epilepsy.Neurobiology of disease · 2023Article
- Early Treatment with Metformin Improves Neurological Outcomes in Lafora Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Lafora disease (LD, OMIM 254780) is a rare fatal neurodegenerative disorder that usually occurs during childhood with generalized tonic-clonic seizures, myoclonus, absences, drop attacks, or visual seizures. Unfortunately, at present, available treatments are only palliatives and no curative drugs are available yet. The hallmark of the disease is the accumulation of insoluble polyglucosan inclusions, called Lafora bodies (LBs), within the neurons but also in heart, muscle, and liver cells. Mouse models lacking functional EPM2A or EPM2B genes (the two major loci related to the disease) recapitulate the Lafora disease phenotype: they accumulate polyglucosan inclusions, show signs of neurodegeneration, and have a dysregulation of protein clearance and endoplasmic reticulum stress response. In this study, we have subjected a mouse model of LD (Epm2b-/-) to different pharmacological interventions aimed to alleviate protein clearance and endoplasmic reticulum stress. We have used two chemical chaperones, trehalose and 4-phenylbutyric acid. In addition, we have used metformin, an activator of AMP-activated protein kinase (AMPK), as it has a recognized neuroprotective role in other neurodegenerative diseases. Here, we show that treatment with 4-phenylbutyric acid or metformin decreases the accumulation of Lafora bodies and polyubiquitin protein aggregates in the brain of treated animals. 4-Phenylbutyric acid and metformin also diminish neurodegeneration (measured in terms of neuronal loss and reactive gliosis) and ameliorate neuropsychological tests of Epm2b-/- mice. As these compounds have good safety records and are already approved for clinical uses on different neurological pathologies, we think that the translation of our results to the clinical practice could be straightforward.
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