Alterations in lipid metabolism gene expression and abnormal lipid accumulation in fibroblast explants from giant axonal neuropathy patients
BACKGROUND: Giant axonal neuropathy (GAN) is a hereditary neurological disorder that affects both central and peripheral nerves. The main pathological hallmark of the disease is abnormal accumulations of intermediate filaments (IFs) in giant axons and other cell types. Mutations in the GAN gene, enc...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2007
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1810559/ https://www.ncbi.nlm.nih.gov/pubmed/17331252 http://dx.doi.org/10.1186/1471-2156-8-6 |
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author | Leung, Conrad L Pang, Yinghua Shu, Chang Goryunov, Dmitry Liem, Ronald KH |
author_facet | Leung, Conrad L Pang, Yinghua Shu, Chang Goryunov, Dmitry Liem, Ronald KH |
author_sort | Leung, Conrad L |
collection | PubMed |
description | BACKGROUND: Giant axonal neuropathy (GAN) is a hereditary neurological disorder that affects both central and peripheral nerves. The main pathological hallmark of the disease is abnormal accumulations of intermediate filaments (IFs) in giant axons and other cell types. Mutations in the GAN gene, encoding gigaxonin, cause the disease. Gigaxonin is important in controlling protein degradation via the ubiquitin-proteasome system. The goal of this study was to examine global alterations in gene expression in fibroblasts derived from newly identified GAN families compared with normal cells. RESULTS: We report the characterization of fibroblast explants obtained from two unrelated GAN patients. We identify three novel putative mutant GAN alleles and show aggregation of vimentin IFs in these fibroblasts. By microarray analysis, we also demonstrate that the expression of lipid metabolism genes of the GAN fibroblasts is disrupted, which may account for the abnormal accumulations of lipid droplets in these cells. CONCLUSION: Our findings suggest that aberrant lipid metabolism in GAN patients may contribute to the progression of the disease. |
format | Text |
id | pubmed-1810559 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-18105592007-03-07 Alterations in lipid metabolism gene expression and abnormal lipid accumulation in fibroblast explants from giant axonal neuropathy patients Leung, Conrad L Pang, Yinghua Shu, Chang Goryunov, Dmitry Liem, Ronald KH BMC Genet Research Article BACKGROUND: Giant axonal neuropathy (GAN) is a hereditary neurological disorder that affects both central and peripheral nerves. The main pathological hallmark of the disease is abnormal accumulations of intermediate filaments (IFs) in giant axons and other cell types. Mutations in the GAN gene, encoding gigaxonin, cause the disease. Gigaxonin is important in controlling protein degradation via the ubiquitin-proteasome system. The goal of this study was to examine global alterations in gene expression in fibroblasts derived from newly identified GAN families compared with normal cells. RESULTS: We report the characterization of fibroblast explants obtained from two unrelated GAN patients. We identify three novel putative mutant GAN alleles and show aggregation of vimentin IFs in these fibroblasts. By microarray analysis, we also demonstrate that the expression of lipid metabolism genes of the GAN fibroblasts is disrupted, which may account for the abnormal accumulations of lipid droplets in these cells. CONCLUSION: Our findings suggest that aberrant lipid metabolism in GAN patients may contribute to the progression of the disease. BioMed Central 2007-03-01 /pmc/articles/PMC1810559/ /pubmed/17331252 http://dx.doi.org/10.1186/1471-2156-8-6 Text en Copyright © 2007 Leung et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Leung, Conrad L Pang, Yinghua Shu, Chang Goryunov, Dmitry Liem, Ronald KH Alterations in lipid metabolism gene expression and abnormal lipid accumulation in fibroblast explants from giant axonal neuropathy patients |
title | Alterations in lipid metabolism gene expression and abnormal lipid accumulation in fibroblast explants from giant axonal neuropathy patients |
title_full | Alterations in lipid metabolism gene expression and abnormal lipid accumulation in fibroblast explants from giant axonal neuropathy patients |
title_fullStr | Alterations in lipid metabolism gene expression and abnormal lipid accumulation in fibroblast explants from giant axonal neuropathy patients |
title_full_unstemmed | Alterations in lipid metabolism gene expression and abnormal lipid accumulation in fibroblast explants from giant axonal neuropathy patients |
title_short | Alterations in lipid metabolism gene expression and abnormal lipid accumulation in fibroblast explants from giant axonal neuropathy patients |
title_sort | alterations in lipid metabolism gene expression and abnormal lipid accumulation in fibroblast explants from giant axonal neuropathy patients |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1810559/ https://www.ncbi.nlm.nih.gov/pubmed/17331252 http://dx.doi.org/10.1186/1471-2156-8-6 |
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