Alexander disease: models, mechanisms, and medicine

Alexander disease is a primary disorder of astrocytes caused by gain-of-function mutations in the gene for glial fibrillary acidic protein (GFAP), which lead to protein aggregation and a reactive astrocyte response, with devastating effects on the central nervous system. Over the past two decades si...

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Veröffentlicht in:Current opinion in neurobiology 2022-02, Vol.72, p.140-147
1. Verfasser: Hagemann, Tracy L.
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description Alexander disease is a primary disorder of astrocytes caused by gain-of-function mutations in the gene for glial fibrillary acidic protein (GFAP), which lead to protein aggregation and a reactive astrocyte response, with devastating effects on the central nervous system. Over the past two decades since the discovery of GFAP as the culprit, several cellular and animal models have been generated, and much has been learned about underlying mechanisms contributing to the disease. Despite these efforts, many aspects of Alexander disease have remained enigmatic, particularly the initiating events in GFAP accumulation and astrocyte pathology, the relation between astrocyte dysfunction and myelin deficits, and the variability in age of onset and disease severity. More recent work in both old and new models has begun to address these complex questions and identify new therapeutics that finally offer the promise of effective treatment.
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subjects Alexander Disease - genetics
Alexander Disease - metabolism
Alexander Disease - pathology
Animals
Astrocytes - metabolism
Central Nervous System - pathology
Glial Fibrillary Acidic Protein - genetics
Glial Fibrillary Acidic Protein - metabolism
Humans
Mutation
Protein Aggregates
title Alexander disease: models, mechanisms, and medicine
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