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...

Descripción completa

Detalles Bibliográficos
Autores principales: Leung, Conrad L, Pang, Yinghua, Shu, Chang, Goryunov, Dmitry, Liem, Ronald KH
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
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
_version_ 1782132602381008896
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
work_keys_str_mv AT leungconradl alterationsinlipidmetabolismgeneexpressionandabnormallipidaccumulationinfibroblastexplantsfromgiantaxonalneuropathypatients
AT pangyinghua alterationsinlipidmetabolismgeneexpressionandabnormallipidaccumulationinfibroblastexplantsfromgiantaxonalneuropathypatients
AT shuchang alterationsinlipidmetabolismgeneexpressionandabnormallipidaccumulationinfibroblastexplantsfromgiantaxonalneuropathypatients
AT goryunovdmitry alterationsinlipidmetabolismgeneexpressionandabnormallipidaccumulationinfibroblastexplantsfromgiantaxonalneuropathypatients
AT liemronaldkh alterationsinlipidmetabolismgeneexpressionandabnormallipidaccumulationinfibroblastexplantsfromgiantaxonalneuropathypatients