Lafora disease: insights into neurodegeneration from plant metabolism

• Published in: Trends in biochemical sciences (Amsterdam. Regular ed.) 2009-12, Vol.34 (12), p.628-639
• Main Authors: Gentry, Matthew S., Dixon, Jack E., Worby, Carolyn A.
• Format: Article
• Language: English
• Subjects: Animals; Carrier Proteins - genetics; Carrier Proteins - physiology; Humans; Lafora Disease - genetics; Lafora Disease - metabolism; Models, Biological; Neurodegenerative Diseases - etiology; Neurodegenerative Diseases - metabolism; Protein Tyrosine Phosphatases, Non-Receptor - genetics; Protein Tyrosine Phosphatases, Non-Receptor - physiology; Ubiquitin-Protein Ligases
• ISSN: 0968-0004; 1362-4326
• DOI: 10.1016/j.tibs.2009.08.002

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.