ArticleMolecular neurobiology2013
Laforin prevents stress-induced polyglucosan body formation and Lafora disease progression in neurons.
Article in Molecular neurobiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Article
- Inactivation of Laforin Phosphatase and Increased Glucose Uptake Underlie Glycogen Synthase-Mediated Neuronal Survival Under Oxidative Stress.Molecular neurobiology · 2025Article
- Glycogen synthase is required for heat shock-mediated autophagy induction in neuronal cells.Biology open · 2025Article
- Lafora progressive myoclonus epilepsy: Disease mechanism and therapeutic attempts.Journal of biosciences · 2024Review
- Mechanisms of Cadmium Neurotoxicity.International journal of molecular sciences · 2023Review
- Increase in brain glycogen levels ameliorates Huntington's disease phenotype and rescues neurodegeneration in Drosophila.Disease models & mechanisms · 2023Article
- Age-Dependent Reduction in the Expression Levels of Genes Involved in Progressive Myoclonus Epilepsy Correlates with Increased Neuroinflammation and Seizure Susceptibility in Mouse Models.Molecular neurobiology · 2022Article
- Wdfy3 regulates glycophagy, mitophagy, and synaptic plasticity.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Stbd1 promotes glycogen clustering during endoplasmic reticulum stress and supports survival of mouse myoblasts.Journal of cell science · 2020Article
- Skeletal Muscle Glycogen Chain Length Correlates with Insolubility in Mouse Models of Polyglucosan-Associated Neurodegenerative Diseases.Cell reports · 2019Article
- Decreased Glycogenolysis byFrontiers in molecular neuroscience · 2019Article
- Lafora disease: from genotype to phenotype.Journal of genetics · 2018Review
- Glycogen synthase protects neurons from cytotoxicity of mutant huntingtin by enhancing the autophagy flux.Cell death & disease · 2018Article
- A novel image-based high-throughput screening assay discovers therapeutic candidates for adult polyglucosan body disease.The Biochemical journal · 2017Article
- Triacylglycerol mimetics regulate membrane interactions of glycogen branching enzyme: implications for therapy.Journal of lipid research · 2017Article
- Does abnormal glycogen structure contribute to increased susceptibility to seizures in epilepsy?Metabolic brain disease · 2015Review
- Laforin-malin complex degrades polyglucosan bodies in concert with glycogen debranching enzyme and brain isoform glycogen phosphorylase.Molecular neurobiology · 2014Article
- Activation of serum/glucocorticoid-induced kinase 1 (SGK1) underlies increased glycogen levels, mTOR activation, and autophagy defects in Lafora disease.Molecular biology of the cell · 2013Article
Corrections and comments
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Authors and funding
10 authors at 7 institutions in 3 countries.
Funding
Abstract
Glycogen, the largest cytosolic macromolecule, is soluble because of intricate construction generating perfect hydrophilic-surfaced spheres. Little is known about neuronal glycogen function and metabolism, though progress is accruing through the neurodegenerative epilepsy Lafora disease (LD) proteins laforin and malin. Neurons in LD exhibit Lafora bodies (LBs), large accumulations of malconstructed insoluble glycogen (polyglucosans). We demonstrated that the laforin-malin complex reduces LBs and protects neuronal cells against endoplasmic reticulum stress-induced apoptosis. We now show that stress induces polyglucosan formation in normal neurons in culture and in the brain. This is mediated by increased glucose-6-phosphate allosterically hyperactivating muscle glycogen synthase (GS1) and is followed by activation of the glycogen digesting enzyme glycogen phosphorylase. In the absence of laforin, stress-induced polyglucosans are undigested and accumulate into massive LBs, and in laforin-deficient mice, stress drastically accelerates LB accumulation and LD. The mechanism through which laforin-malin mediates polyglucosan degradation remains unclear but involves GS1 dephosphorylation by laforin. Our work uncovers the presence of rapid polyglucosan metabolism as part of the normal physiology of neuroprotection. We propose that deficiency in the degradative phase of this metabolism, leading to LB accumulation and resultant seizure predisposition and neurodegeneration, underlies LD.
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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.