Role of Astrocytes in the Pathophysiology of Lafora Disease and Other Glycogen Storage Disorders

Lafora disease is a rare disorder caused by loss of function mutations in either the EPM2A or NHLRC1 gene. The initial symptoms of this condition are most commonly epileptic seizures, but the disease progresses rapidly with dementia, neuropsychiatric symptoms, and cognitive deterioration and has a fatal outcome within 5-10 years after onset. The hallmark of the disease is the accumulation of poorly branched glycogen in the form of aggregates known as Lafora bodies in the brain and other tissues. Several reports have demonstrated that the accumulation of this abnormal glycogen underlies all the pathologic traits of the disease. For decades, Lafora bodies were thought to accumulate exclusively in neurons. However, it was recently identified that most of these glycogen aggregates are present in astrocytes. Importantly, astrocytic Lafora bodies have been shown to contribute to pathology in Lafora disease. These results identify a primary role of astrocytes in the pathophysiology of Lafora disease and have important implications for other conditions in which glycogen abnormally accumulates in astrocytes, such as Adult Polyglucosan Body disease and the buildup of Corpora amylacea in aged brains.

Automated summary

Lafora disease is a rare disorder caused by mutations in the EPM2A or NHLRC1 gene, resulting in the accumulation of poorly branched glycogen known as Lafora bodies in the brain and other tissues. While it was previously believed that these glycogen aggregates only accumulated in neurons, recent research has shown that astrocytes also play a significant role in the pathology of the disease. Understanding the involvement of astrocytes in Lafora disease has important implications for other conditions characterized by abnormal glycogen accumulation in astrocytes, such as Adult Polyglucosan Body disease and Corpora amylacea buildup in aged brains.