2026-04-14T04:35:38Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1770832025-12-04T19:04:19Zcom_2072_1057col_2072_478777col_2072_478781col_2072_478902col_2072_478906col_2072_478908col_2072_478917

urn:hdl:2445/177083 Astrocytic glycogen accumulation drives the pathophysiology of neurodegeneration in Lafora disease Duran, Jordi Hervera Abad, Arnau Markussen, Kia H. Varea, Olga López-Soldado, Iliana Sun, Ramon C. Río Fernández, José Antonio del Gentry, Matthew S. Guinovart, Joan J. (Joan Josep), 1947- Epilèpsia Glicogen Malalties neurodegeneratives Epilepsy Glycogen Neurodegenerative Diseases The hallmark of Lafora disease, a fatal neurodegenerative disorder, is the accumulation of intracellular glycogen aggregates, called Lafora bodies. Until recently, it was widely believed that brain Lafora bodies were present exclusively in neurons and thus that Lafora disease pathology derived from their accumulation in this cell population. However, recent evidence indicates that Lafora bodies are also present in astrocytes. To define the role of astrocytic Lafora bodies in Lafora disease pathology, we deleted glycogen synthase specifically from astrocytes in a mouse model of the disease (malinKO). Strikingly, blocking glycogen synthesis in astrocytes-thus impeding Lafora bodies accumulation in this cell type-prevented the increase in neurodegeneration markers, autophagy impairment, and metabolic changes characteristic of the malinKO model. Conversely, mice that overaccumulate glycogen in astrocytes showed an increase in these markers. These results unveil the deleterious consequences of the deregulation of glycogen metabolism in astrocytes and change the perspective that Lafora disease is caused solely by alterations in neurons 2021-05-10T07:10:12Z 2022-04-02T05:10:19Z 2021-04-02 2021-05-07T08:38:22Z info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Reproducció del document publicat a: https://doi.org/10.1093/brain/awab110 Brain, 2021 https://doi.org/10.1093/brain/awab110 (c) Duran et al., 2021 info:eu-repo/semantics/openAccess Oxford University Press Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)