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12541_6503311_duran_et_al_brain_2021.pdf (3.86 MB)

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2021-04-02

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/177083

Astrocytic glycogen accumulation drives the pathophysiology of neurodegeneration in Lafora disease

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https://doi.org/10.1093/brain/awab110

Resum

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

Matèries

Epilèpsia, Glicogen, Malalties neurodegeneratives

Matèries (anglès)

Epilepsy, Glycogen, Neurodegenerative Diseases

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Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))
Articles publicats en revistes (Institut de Neurociències (UBNeuro))
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

Citació

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). Astrocytic glycogen accumulation drives the pathophysiology of neurodegeneration in Lafora disease. _Brain_. 2021. [consulta: 21 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/177083]

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