Web of Science: 49 cites, Scopus: 49 cites, Google Scholar: cites,
Neuronal glycogen synthesis contributes to physiological aging
Sinadinos, Christopher (Institut de Recerca Biomèdica de Lleida)
Valles-Ortega, Jordi (Institut de Recerca Biomèdica)
Boulan, Laura (Institut de Recerca Biomèdica)
Solsona, Estel (Institut de Recerca Biomèdica)
Tevy, Maria F. (Institut de Recerca Biomèdica)
Márquez, Mercedes (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Duran, Jordi (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)
Lopez-Iglesias, Carmen (Universitat de Barcelona. Electron Cryo-Microscopy Unit, Scientific and Technological Centres)
Calbó, Joaquim (Institut de Recerca Biomèdica)
Blasco, Ester (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Pumarola i Batlle, Martí (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Milán, Marco (Institució Catalana de Recerca i Estudis Avançats (ICREA))
Guinovart Cirera, Joan J. (Universitat de Barcelona. Departament de Bioquímica i Biologia Molecular)

Data: 2014
Resum: 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.
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: Article ; recerca ; Versió publicada
Publicat a: Aging Cell, Vol. 13, Núm. 5 (2014) , p. 935-945, ISSN 1474-9726

Adreça alternativa: https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12254
DOI: 10.1111/acel.12254
PMID: 25059425

11 p, 2.3 MB

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