Microglial activation precedes acute neurodegeneration in Sandhoff disease and is suppressed by bone marrow transplantation
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- Ryuichi Wada
- Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892; and Department of Medical Genetics, Children's National Medical Center, Washington, DC 20010
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- Cynthia J. Tifft
- Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892; and Department of Medical Genetics, Children's National Medical Center, Washington, DC 20010
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- Richard L. Proia
- Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892; and Department of Medical Genetics, Children's National Medical Center, Washington, DC 20010
書誌事項
- 公開日
- 2000-09-26
- DOI
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- 10.1073/pnas.97.20.10954
- 公開者
- Proceedings of the National Academy of Sciences
この論文をさがす
説明
<jats:p> Sandhoff disease is a lysosomal storage disorder characterized by the absence of β-hexosaminidase and storage of G <jats:sub>M2</jats:sub> ganglioside and related glycolipids in the central nervous system. The glycolipid storage causes severe neurodegeneration through a poorly understood pathogenic mechanism. In symptomatic Sandhoff disease mice, apoptotic neuronal cell death was prominent in the caudal regions of the brain. cDNA microarray analysis to monitor gene expression during neuronal cell death revealed an upregulation of genes related to an inflammatory process dominated by activated microglia. Activated microglial expansion, based on gene expression and histologic analysis, was found to precede massive neuronal death. Extensive microglia activation also was detected in a human case of Sandhoff disease. Bone marrow transplantation of Sandhoff disease mice suppressed both the explosive expansion of activated microglia and the neuronal cell death without detectable decreases in neuronal G <jats:sub>M2</jats:sub> ganglioside storage. These results suggest a mechanism of neurodegeneration that includes a vigorous inflammatory response as an important component. Thus, this lysosomal storage disease has parallels to other neurodegenerative disorders, such as Alzheimer's and prion diseases, where inflammatory processes are believed to participate directly in neuronal cell death. </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 97 (20), 10954-10959, 2000-09-26
Proceedings of the National Academy of Sciences
