2026-04-18T05:59:36Zhttps://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
RECERCAT author Duran, Jordi author Hervera Abad, Arnau author Markussen, Kia H. author Varea, Olga author López-Soldado, Iliana author Sun, Ramon C. author Río Fernández, José Antonio del author Gentry, Matthew S. author Guinovart, Joan J. (Joan Josep), 1947- 2021-05-10T07:10:12Z2022-04-02T05:10:19Z2021-04-022021-05-07T08:38:22Z 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 (c) Duran et al., 2021 info:eu-repo/semantics/openAccess Epilèpsia Glicogen Malalties neurodegeneratives Epilepsy Glycogen Neurodegenerative Diseases Astrocytic glycogen accumulation drives the pathophysiology of neurodegeneration in Lafora disease info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion