Neuronal glycogen synthesis contributes to physiological aging
| Autor: | Estel Solsona, Carmen López-Iglesias, Martí Pumarola, Maria Florencia Tevy, Ester Blasco, Joaquim Calbó, Christopher Sinadinos, Marco Milán, Jordi Valles-Ortega, Mercedes Márquez, Laura Boulan, Jordi Duran, Joan J. Guinovart |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Aging medicine.medical_specialty Mice Transgenic Biology Protein aggregation Polysaccharide protein aggregation Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Animals Humans corpora amylacea Glycogen synthase Glucans Heat-Shock Proteins 030304 developmental biology Neurons chemistry.chemical_classification 0303 health sciences Glycogen Neurodegeneration Brain Original Articles stress response Cell Biology Human brain medicine.disease Mice Inbred C57BL Drosophila melanogaster Glycogen Synthase Endocrinology medicine.anatomical_structure chemistry glycogen biology.protein Drosophila Female Corpora amylacea Laforin 030217 neurology & neurosurgery |
| Zdroj: | Aging Cell Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona |
| ISSN: | 1474-9726 1474-9718 |
| DOI: | 10.1111/acel.12254 |
| Popis: | Glycogen is a branched polymer of glucose and the carbohydrate energy store for animal cells. In the brain, it is essentially found in glial cells, although it is also present in minute amounts in neurons. In humans, loss-of-function mutations in laforin and malin, proteins involved in suppressing glycogen synthesis, induce the presence of high numbers of insoluble polyglucosan bodies in neuronal cells. Known as Lafora bodies (LBs), these deposits result in the aggressive neurodegeneration seen in Lafora's disease. Polysaccharide-based aggregates, called corpora amylacea (CA), are also present in the neurons of aged human brains. Despite the similarity of CA to LBs, the mechanisms and functional consequences of CA formation are yet unknown. Here, we show that wild-type laboratory mice also accumulate glycogen-based aggregates in the brain as they age. These structures are immunopositive for an array of metabolic and stress-response proteins, some of which were previously shown to aggregate in correlation with age in the human brain and are also present in LBs. Remarkably, these structures and their associated protein aggregates are not present in the aged mouse brain upon genetic ablation of glycogen synthase. Similar genetic intervention in Drosophila prevents the accumulation of glycogen clusters in the neuronal processes of aged flies. Most interestingly, targeted reduction of Drosophila glycogen synthase in neurons improves neurological function with age and extends lifespan. These results demonstrate that neuronal glycogen accumulation contributes to physiological aging and may therefore constitute a key factor regulating age-related neurological decline in humans. |
| Databáze: | OpenAIRE |
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