Astrocytic glycogen accumulation drives the pathophysiology of neurodegeneration in Lafora disease

Jordi Duran, Arnau Hervera, Kia H. Markussen, Olga Varea, Iliana López-Soldado, Ramon C. Sun, Jose Antonio Del Río, Matthew S. Gentry, Joan J. Guinovart

Research output: Indexed journal article Articlepeer-review

18 Citations (Scopus)


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 over-accumulate 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.

Original languageEnglish
Pages (from-to)2349-2360
Number of pages12
Issue number8
Publication statusPublished - 1 Aug 2021
Externally publishedYes


  • Epilepsy
  • Glycogen
  • Lafora disease
  • Neurodegeneration
  • Neuroinflammation


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