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Title: Astrocytic glycogen accumulation drives the pathophysiology of neurodegeneration in Lafora disease
Author: 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-
Keywords: Epilèpsia
Malalties neurodegeneratives
Neurodegenerative diseases
Issue Date: 2-Apr-2021
Publisher: Oxford University Press
Abstract: 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
Note: Reproducció del document publicat a:
It is part of: Brain, 2021
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Appears in Collections:Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))
Articles publicats en revistes (Institut de Neurociències (UBNeuro))
Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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