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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 f...

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Detalles Bibliográficos
Autor principal: Duran, Jordi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10000527/
https://www.ncbi.nlm.nih.gov/pubmed/36899857
http://dx.doi.org/10.3390/cells12050722
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author Duran, Jordi
author_facet Duran, Jordi
author_sort Duran, Jordi
collection PubMed
description 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.
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spelling pubmed-100005272023-03-11 Role of Astrocytes in the Pathophysiology of Lafora Disease and Other Glycogen Storage Disorders Duran, Jordi Cells Review 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. MDPI 2023-02-24 /pmc/articles/PMC10000527/ /pubmed/36899857 http://dx.doi.org/10.3390/cells12050722 Text en © 2023 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Duran, Jordi
Role of Astrocytes in the Pathophysiology of Lafora Disease and Other Glycogen Storage Disorders
title Role of Astrocytes in the Pathophysiology of Lafora Disease and Other Glycogen Storage Disorders
title_full Role of Astrocytes in the Pathophysiology of Lafora Disease and Other Glycogen Storage Disorders
title_fullStr Role of Astrocytes in the Pathophysiology of Lafora Disease and Other Glycogen Storage Disorders
title_full_unstemmed Role of Astrocytes in the Pathophysiology of Lafora Disease and Other Glycogen Storage Disorders
title_short Role of Astrocytes in the Pathophysiology of Lafora Disease and Other Glycogen Storage Disorders
title_sort role of astrocytes in the pathophysiology of lafora disease and other glycogen storage disorders
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10000527/
https://www.ncbi.nlm.nih.gov/pubmed/36899857
http://dx.doi.org/10.3390/cells12050722
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