Glycogen Storage Diseases and Myoclonus

Sequence determinants of pathogenicity in glucose-6-phosphatase linked to glycogen storage disease type 1a

The paper uses AlphaMissense and experimental assays to analyze 78 G6PC1 variants, identifying stability and allosteric modulation as key pathogenic mechanisms.

The liver compensates for zonal loss of glucose 6-phosphatase to prevent glycogen storage disease

This study shows that localized loss of G6pc1 in liver zones causes local glycogen accumulation but not systemic disease, highlighting organ-wide compensation for metabolic homeostasis.

Drosophila melanogaster lactate dehydrogenase deficiency recapitulates the exercise intolerance of human glycogen storage disease type XI

This study shows that loss of lactate dehydrogenase in Drosophila causes exercise intolerance and diet-dependent lethality, mirroring human LDH-A deficiency symptoms.

Unifying the communities of early-onset glycogen storage disease type IV and adult polyglucosan body disease through a genetic prevalence study of GBE1-related disease

This paper estimates the global prevalence of GSD IV and APBD by analyzing GBE1 variants across nine genetic groups, finding 1 in 235,784 individuals are affected.

Proteomics profiling of serum and liver in GSD Ia and Ib patients: insights into complication mechanisms and circulation biomarkers

This study uses proteomics to compare serum and liver samples from GSD Ia and Ib patients, identifying subtype-specific biomarkers and pathways linked to disease complications.

The Pgb1 locus controls glycogen aggregation in astrocytes of the aged hippocampus without impacting cognitive function

The paper identifies the Pgb1 locus as controlling glycogen aggregation in aged hippocampal astrocytes without affecting cognitive function.

Neuronal Hyperexcitability: A Key to Unravelling Hippocampal Synaptic Dysfunctions in Lafora Disease

This study investigates early molecular mechanisms of Lafora disease using a mouse model, finding that neuronal hyperexcitability and impaired synaptic plasticity emerge early and can be mitigated by CBD treatment.

Cell modeling and rescue of a novel non-coding genetic cause of Glycogen Storage Disease IX

The paper identifies a non-coding variant causing GSD IX γ2, validates its splicing effects, and demonstrates reversal using antisense oligonucleotides.

The ABCs of Cyanobacterial Glycogen: In Vitro Modelling of Glycogen Synthesis and Functional Divergence of Glycogen Synthases in Synechocystis sp. PCC 6803

The paper reconstitutes glycogen synthesis in vitro using Synechocystis enzymes to show how different synthases produce distinct glycogen structures and functions.

FSCN1-Mediated Hepatic Gluconeogenesis Is Indispensable for Neonatal Mice Survival

This study shows FSCN1 is essential for neonatal survival by maintaining hepatic glucose production from glycerol, as Fscn1 knockout mice die of hypoglycemia despite normal insulin-regulated gluconeogenesis.

Novel mouse model reveals neurodevelopmental origin of PMM2-CDG brain pathology

This study creates a mouse model of PMM2-CDG by selectively removing PMM2 from neural precursor cells, revealing cerebellar hypoplasia and ataxia, and showing molecular disturbances in the cerebellum that mirror human disease.

PPP1R3B is a metabolic switch that shifts hepatic energy storage from lipid to glycogen

This paper investigates the role of PPP1R3B in hepatic metabolism, finding it acts as a switch that promotes glycogen storage over lipid accumulation, with implications for metabolic diseases.

Glial alterations in the glutamatergic and GABAergic signaling pathways in a mouse model of Lafora disease, a severe form of progressive myoclonus epilepsy

The paper investigates glial alterations in glutamatergic and GABAergic signaling pathways in a mouse model of Lafora disease, finding dysregulated receptor subunits and increased GABA transporter levels in glial cells.

Clinicopathologic Dissociation: Robust Lafora Body Accumulation in Malin KO Mice Without Observable Changes in Home-cage Behavior

This study shows that malin-deficient mice accumulate Lafora bodies without observable neurobehavioral decline, suggesting a delay between LB accumulation and clinical symptoms.

Gene replacement therapy for Lafora disease in the Epm2a-/- mouse model

This study uses gene replacement therapy in Epm2a-/- mice to treat Lafora disease, showing improvements in neurological symptoms and reduced Lafora body formation.

Disease-associated programming of cell memory in glycogen storage disorder type 1a

This paper shows that GSD1a patient fibroblasts retain a reversible disease phenotype in vitro, driven by epigenetic and transcriptional changes, and that a drug can reverse these effects.

Lack of p62 impairs glycogen aggregation and exacerbates pathology in a mouse model of myoclonic epilepsy of Lafora

This study shows that p62 is involved in Lafora body formation and that its absence reduces glycogen aggregation in muscle and heart but worsens brain pathology in a mouse model of Lafora disease.

Gys1 antisense therapy rescues neuropathological bases of murine Lafora disease

This study shows that Gys1 antisense therapy reduces Lafora body formation and neuroinflammation in mouse models of Lafora disease.

Targeting Gys1 with AAV-SaCas9 decreases pathogenic polyglucosan bodies and neuroinflammation in Adult Polyglucosan Body and Lafora disease mouse models

This study uses AAV-delivered CRISPR/Cas9 to target Gys1 in mouse models of neurodegenerative diseases, reducing polyglucosan bodies and neuroinflammation.

The motor neuron-like cell line NSC-34 and its parent cell line N18TG2 have glycogen that is degraded under cellular stress

The paper investigates glycogen metabolism in neuronal cell lines NSC-34 and N18TG2, showing that glycogen is degraded under hypoxia, oxidative, and acidic stress.

A new drug candidate for glycogen storage disorders enhances glycogen catabolism: Lessons from Adult Polyglucosan Body Disease models

This study demonstrates that 144DG11 improves survival and motor function in APBD mouse models by promoting autophagic glycogen catabolism through LAMP1 interaction.

Scaffolding protein IQ motif containing GTPase activating protein 2 (IQGAP2) regulates glycogen metabolism

This study shows that IQGAP2 deletion in mice affects glycogen synthesis by altering GSK3 phosphorylation and β-catenin levels, leading to reduced glycogen storage.

Yeast Models Of Phosphomannomutase 2 Deficiency, A Congenital Disorder Of Glycosylation

This paper uses yeast models to study PMM2-CDG mutations, identifies compounds that suppress growth defects, and suggests pathogenicity mechanisms in human patients.

Deficiency of the E3 Ubiquitin Ligase RBCK1 Causes Diffuse Brain Polyglucosan Accumulation and Neurodegeneration

This study shows that RBCK1 deficiency in mice leads to brain polyglucosan accumulation and neurodegeneration, similar to Lafora disease but with distinct regional and subcellular features.