A5082015261- Glycogen Storage Diseases and Myoclonus
- Protein Tyrosine Phosphatases
- Genetics and Neurodevelopmental Disorders
- Lysosomal Storage Disorders Research
- Carbohydrate Chemistry and Synthesis
- Genetic Syndromes and Imprinting
- Neurological disorders and treatments
- Memory and Neural Mechanisms
- Epilepsy research and treatment
- Neuroscience and Neuropharmacology Research
- Growth Hormone and Insulin-like Growth Factors
- Neurogenetic and Muscular Disorders Research
- Parkinson's Disease Mechanisms and Treatments
- Enzyme Production and Characterization
- Pancreatic function and diabetes
- Zoonotic diseases and public health
- RNA regulation and disease
- Amyotrophic Lateral Sclerosis Research
- Yersinia bacterium, plague, ectoparasites research
- Salmonella and Campylobacter epidemiology
- Calpain Protease Function and Regulation
- Glycosylation and Glycoproteins Research
- interferon and immune responses
Institute for Research in Biomedicine
2020-2023
University of Kentucky
2014-2021
Epilepsy Foundation
2018
Lafora disease (LD) is a fatal childhood epilepsy caused by recessive mutations in either the EPM2A or EPM2B gene. A hallmark of LD intracellular accumulation insoluble polysaccharide deposits known as bodies (LBs) brain and other tissues. In mouse models, genetic reduction glycogen synthesis eliminates LB formation rescues neurological phenotype. Therefore, LBs have become therapeutic target for ameliorating LD. Herein, we demonstrate that human pancreatic α-amylase degrades LBs. We fused...
Abstract Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of motor neurons in spinal cord. Glial cells, including astrocytes and microglia, have been shown to contribute neurodegeneration ALS, metabolic dysfunction plays an important role progression disease. Glycogen soluble polymer glucose found at low levels central nervous system that memory formation, synaptic plasticity, prevention seizures. However, its accumulation...
Lafora disease (LD) is a fatal childhood dementia characterized by progressive myoclonic epilepsy manifesting in the teenage years, rapid neurological decline, and death typically within ten years of onset. Mutations either EPM2A, encoding glycogen phosphatase laforin, or EPM2B, E3 ligase malin, cause LD. Whole exome sequencing has revealed many EPM2A variants associated with late-onset slower progression. We established an empirical pipeline for characterizing functional consequences...
Lafora disease (LD) is a fatal childhood-onset dementia characterized by the extensive accumulation of glycogen aggregates-the so-called Bodies (LBs)-in several organs. The LBs in brain underlies neurological phenotype disease. are composed abnormal and various associated proteins, including p62, an autophagy adaptor that participates aggregation clearance misfolded proteins. To study role p62 formation its participation pathology LD, we generated mouse model (malinKO) lacking p62. Deletion...
The gene that encodes laforin, a dual-specificity phosphatase with carbohydrate-binding module, is mutated in Lafora disease (LD). LD an autosomal recessive, fatal progressive myoclonus epilepsy characterized by the intracellular buildup of insoluble, hyperphosphorylated glycogen-like particles, called bodies. Laforin dephosphorylates glycogen and other glucans vitro, but structural basis its activity remains unknown. Recombinant human laforin when expressed purified from E. coli largely...
Abstract Lafora disease (LD) is a fatal childhood epilepsy and non-classical glycogen storage disorder with no effective therapy or cure. LD caused by recessive mutations in the EPM2A EPM2B genes that encode phosphatase laforin an E3 ubiquitin ligase malin, respectively. A hallmark of intracellular accumulation abnormal insoluble α-linked polysaccharide deposits known as bodies (LBs) several tissues, including most regions brain. In mouse models LD, genetic reduction synthesis eliminates LB...
ABSTRACT Lafora disease (LD) is a fatal, insidious metabolic disorder characterized by progressive myoclonic epilepsy manifesting in the teenage years, rapid neurological decline, and death typically within ten years of onset. Mutations either EPM2A , encoding glycogen phosphatase laforin, or EPM2B E3 ligase malin, cause LD. Whole exome sequencing has revealed many variants associated with late-onset slower progression. We established an empirical pipeline for characterizing laforin missense...
ABSTRACT Brain glycogen is mainly stored in astrocytes. However, recent studies both vitro and vivo indicate that also plays important roles neurons. By conditional deletion of synthase (GYS1), we previously developed a mouse model entirely devoid the central nervous system (GYS1 Nestin-KO ). These mice displayed altered electrophysiological properties hippocampus increased susceptibility to kainate-induced seizures. To understand which these functions related astrocytic glycogen, present...
Lafora disease (LD) is a fatal childhood dementia characterized by progressive myoclonic epilepsy manifesting in the teenage years, rapid neurological decline, and death typically within ten years of onset. Mutations either EPM2A, encoding glycogen phosphatase laforin, or EPM2B, E3 ligase malin, cause LD. Whole exome sequencing has revealed many EPM2A variants associated with late-onset slower progression. We established an empirical pipeline for characterizing functional consequences...
Glycogen is the major form of carbohydrate storage in mammals and a dynamic participant brain energetics. Slight aberrations glycogen metabolism induce neuronal apoptosis; thus must be highly regulated. Lafora disease (LD) recessive neurodegenerative disorder that manifests as single seizure during adolescence followed by progressive central nervous system degeneration death within ten years. Mutations phosphatase laforin lead to accumulation neurotoxic, hyperphosphorylated known bodies,...
Glycogen is the major mammalian glucose storage cache and critical for energy homeostasis. synthesis in neurons must be tightly controlled, due to neuronal sensitivity perturbations glycogen metabolism. Lafora disease (LD) a fatal, congenital, neurodegenerative epilepsy. Mutations gene encoding phosphatase laforin result hyperphosphorylated that forms water‐insoluble inclusions called bodies (LBs). LBs induce apoptosis are causative agent of LD. The mechanism dephosphorylation by dysfunction...