Lafora disease: insights into neurodegeneration from plant metabolism.
Reversible phosphorylation modulates nearly every step of glycogenesis and glycogenolysis. Multiple metabolic disorders are the result of defective enzymes that control these phosphorylation events, enzymes that were identified biochemically before the advent of the molecular biology era. Lafora disease is a metabolic disorder resulting in accumulation of water-insoluble glucan in the cytoplasm, and manifests as a debilitating neurodegeneration that ends with the death of the patient. Unlike most metabolic disorders, the link between Lafora disease and metabolism has not been defined in almost 100 years. The results of recent studies with mammalian cells, mouse models, eukaryotic algae, and plants have begun to define the molecular mechanisms that cause Lafora disease. The emerging theme identifies a new phosphorylation substrate in glycogen metabolism, the glucan itself.
Gentry
Matthew S
MS
Department of Molecular and Cellular Biochemistry and Center for Structural Biology, University of Kentucky, Lexington, KY 40536-0509, USA. matthew.gentry@uky.edu
Dixon
Jack E
JE
Worby
Carolyn A
CA
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D020192:Lafora Disease / Q000235:genetics* / Q000378:metabolism*; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000378:metabolism*; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics / Q000502:physiology; D044767:Ubiquitin-Protein Ligases
D002352:Carrier Proteins; C478960:NHLRC1 protein, human; D044767:Ubiquitin-Protein Ligases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C114990:EPM2A protein, human