ArticleAnnals of clinical and translational neurology2020
GYS1 or PPP1R3C deficiency rescues murine adult polyglucosan body disease.
Article in Annals of clinical and translational neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 23 citations in OpenAlex.
- Neurological glycogen storage diseases and emerging therapeutics.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Natural history study of hepatic glycogen storage disease type IV and comparison to Gbe1ys/ys model.JCI insight · 2024Article
- Myofiber-type-dependent 'boulder' or 'multitudinous pebble' formations across distinct amylopectinoses.Acta neuropathologica · 2024Article
- Small-molecule inhibition of glycogen synthase 1 for the treatment of Pompe disease and other glycogen storage disorders.Science translational medicine · 2024Article
- Polyglucosan body disease in an aged chimpanzee (Pan troglodytes).Neuropathology : official journal of the Japanese Society of Neuropathology · 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
- Role of Astrocytes in the Pathophysiology of Lafora Disease and Other Glycogen Storage Disorders.Cells · 2023Review
- Proteomic investigations of adult polyglucosan body disease: insights into the pathobiology of a neurodegenerative disorder.Frontiers in neurology · 2023Article
- Glycogen synthase downregulation rescues the amylopectinosis of murine RBCK1 deficiency.Brain : a journal of neurology · 2022Article
- Molecular basis for the regulation of human glycogen synthase by phosphorylation and glucose-6-phosphate.Nature structural & molecular biology · 2022Article
- LUBAC: a new player in polyglucosan body disease.Biochemical Society transactions · 2021Review
- Targeting Gys1 with AAV-SaCas9 Decreases Pathogenic Polyglucosan Bodies and Neuroinflammation in Adult Polyglucosan Body and Lafora Disease Mouse Models.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- miR-140-5p Aggravates Insulin Resistance via Directly Targeting GYS1 and PPP1CC in Insulin-Resistant HepG2 Cells.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Article
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
Abstract
objectiveAdult polyglucosan body disease (APBD) is an adult-onset neurological variant of glycogen storage disease type IV. APBD is caused by recessive mutations in the glycogen branching enzyme gene, and the consequent accumulation of poorly branched glycogen aggregates called polyglucosan bodies in the nervous system. There are presently no treatments for APBD. Here, we test whether downregulation of glycogen synthesis is therapeutic in a mouse model of the disease.
methodsWe characterized the effects of knocking out two pro-glycogenic proteins in an APBD mouse model. APBD mice were crossed with mice deficient in glycogen synthase (GYS1), or mice deficient in protein phosphatase 1 regulatory subunit 3C (PPP1R3C), a protein involved in the activation of GYS1. Phenotypic and histological parameters were analyzed and glycogen was quantified.
resultsAPBD mice deficient in GYS1 or PPP1R3C demonstrated improvements in life span, morphology, and behavioral assays of neuromuscular function. Histological analysis revealed a reduction in polyglucosan body accumulation and of astro- and micro-gliosis in the brains of GYS1- and PPP1R3C-deficient APBD mice. Brain glycogen quantification confirmed the reduction in abnormal glycogen accumulation. Analysis of skeletal muscle, heart, and liver found that GYS1 deficiency reduced polyglucosan body accumulation in all three tissues and PPP1R3C knockout reduced skeletal muscle polyglucosan bodies.
interpretationGYS1 and PPP1R3C are effective therapeutic targets in the APBD mouse model. These findings represent a critical step toward the development of a treatment for APBD and potentially other glycogen storage disease type IV patients.
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