ArticleCell death & disease2018
Glycogen synthase protects neurons from cytotoxicity of mutant huntingtin by enhancing the autophagy flux.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Glycogen drives the sensory activation of POMC neurons.Nature metabolism · 2026Article
- Acetyl-CoA availability regulates neuronal metabolism, growth, and synaptic activity.bioRxiv : the preprint server for biology · 2026Article
- Inactivation of Laforin Phosphatase and Increased Glucose Uptake Underlie Glycogen Synthase-Mediated Neuronal Survival Under Oxidative Stress.Molecular neurobiology · 2025Article
- Neural Metabolic Networks: Key Elements of Healthy Brain Function.Journal of neurochemistry · 2025Review
- Glycogen synthase is required for heat shock-mediated autophagy induction in neuronal cells.Biology open · 2025Article
- Brain Metabolism in Health and Neurodegeneration: The Interplay Among Neurons and Astrocytes.Cells · 2024Review
- Neurological glycogen storage diseases and emerging therapeutics.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- 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
- Intracellular energy controls dynamics of stress-induced ribonucleoprotein granules.Nature communications · 2022Article
- Lack of p62 Impairs Glycogen Aggregation and Exacerbates Pathology in a Mouse Model of Myoclonic Epilepsy of Lafora.Molecular neurobiology · 2022Article
- Alterations in brain glycogen levels influence life-history traits and reduce the lifespan in female Drosophila melanogaster.Biology open · 2021Article
- Emerging roles of N-linked glycosylation in brain physiology and disorders.Trends in endocrinology and metabolism: TEM · 2021Review
- 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
- Adaptive responses to neurodegenerative stress in glaucoma.Progress in retinal and eye research · 2021Review
- When Good Kinases Go Rogue: GSK3, p38 MAPK and CDKs as Therapeutic Targets for Alzheimer's and Huntington's Disease.International journal of molecular sciences · 2021Review
- Gauging the role and impact of drug interactions and repurposing in neurodegenerative disorders.Current research in pharmacology and drug discovery · 2021Review
- Glycogen: the missing link in neuronal autophagy?Autophagy · 2020Review
- A single-cell Raman-based platform to identify developmental stages of human pluripotent stem cell-derived neurons.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Healthy neurons do not store glycogen while they do possess the machinery for the glycogen synthesis albeit at an inactive state. Neurons in the degenerating brain, however, are known to accumulate glycogen, although its significance was not well understood. Emerging reports present contrasting views on neuronal glycogen synthesis; a few reports demonstrate a neurotoxic effect of glycogen while a few others suggest glycogen to be neuroprotective. Thus, the specific role of glycogen and glycogen synthase in neuronal physiology is largely unexplored. Using cellular and animal models of Huntington's disease, we show here that the overexpression of cytotoxic mutant huntingtin protein induces glycogen synthesis in the neurons by activating glycogen synthase and the overexpressed glycogen synthase protected neurons from the cytotoxicity of the mutant huntingtin. Exposure of neuronal cells to proteasomal blockade and oxidative stress also activate glycogen synthase to induce glycogen synthesis and to protect against stress-induced neuronal death. We show that the glycogen synthase plays an essential and inductive role in the neuronal autophagic flux, and helps in clearing the cytotoxic huntingtin aggregate. We also show that the increased neuronal glycogen inhibits the aggregation of mutant huntingtin, and thus could directly contribute to its clearance. Finally, we demonstrate that excessive autophagy flux is the molecular basis of cell death caused by the activation of glycogen synthase in unstressed neurons. Taken together, our results thus provide a novel function for glycogen synthase in proteolytic processes and offer insight into the role of glycogen synthase and glycogen in both survival and death of the neurons.
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