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Transcriptome Profiling Following Neuronal and Glial Expression of ALS-Linked SOD1 in Drosophila

Amyotrophic lateral sclerosis (ALS) generally is a late-onset neurodegenerative disease. Mutations in the Cu/Zn superoxide dismutase 1 (SOD1) gene account for approximately 20% of familial ALS and 2% of all ALS cases. Although a number of hypotheses have been proposed to explain mutant SOD1 toxicity...

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Autores principales: Kumimoto, Emily L., Fore, Taylor R., Zhang, Bing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Genetics Society of America 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3618356/
https://www.ncbi.nlm.nih.gov/pubmed/23550139
http://dx.doi.org/10.1534/g3.113.005850
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author Kumimoto, Emily L.
Fore, Taylor R.
Zhang, Bing
author_facet Kumimoto, Emily L.
Fore, Taylor R.
Zhang, Bing
author_sort Kumimoto, Emily L.
collection PubMed
description Amyotrophic lateral sclerosis (ALS) generally is a late-onset neurodegenerative disease. Mutations in the Cu/Zn superoxide dismutase 1 (SOD1) gene account for approximately 20% of familial ALS and 2% of all ALS cases. Although a number of hypotheses have been proposed to explain mutant SOD1 toxicity, the molecular mechanisms of the disease remain unclear. SOD1-linked ALS is thought to function in a non–cell-autonomous manner such that motoneurons are critical for the onset, and glia contribute to progression of the disease. Recently, it has been shown in Drosophila melanogaster that expression of human SOD1 in a subset of neuronal cells causes synaptic transmission defects, modified motor function, and altered sensitivity to compounds that induce oxidative stress. Here we used the Gal4-UAS (Upstream Activation Sequence) system to further characterize flies expressing wild-type Drosophila SOD1 (dSOD1) and the mutant human SOD1(G85R) (G85R) allele in motoneurons and glia. Cell-specific expression of both dSOD1 and G85R was found to influence lifespan, affect sensitivity to hydrogen peroxide, and alter lipid peroxidation levels. To better understand the genetic consequences of G85R expression in motoneurons and glia, we conducted microarray analysis of both young flies (5 days old) and old flies (45 days old) expressing G85R selectively in motoneurons or glia and concurrently in motoneurons and glia. Results from this microarray experiment identified candidate genes for further investigation and may help elucidate the individual and combined contributions of motoneurons and glia in ALS.
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spelling pubmed-36183562013-04-08 Transcriptome Profiling Following Neuronal and Glial Expression of ALS-Linked SOD1 in Drosophila Kumimoto, Emily L. Fore, Taylor R. Zhang, Bing G3 (Bethesda) Investigations Amyotrophic lateral sclerosis (ALS) generally is a late-onset neurodegenerative disease. Mutations in the Cu/Zn superoxide dismutase 1 (SOD1) gene account for approximately 20% of familial ALS and 2% of all ALS cases. Although a number of hypotheses have been proposed to explain mutant SOD1 toxicity, the molecular mechanisms of the disease remain unclear. SOD1-linked ALS is thought to function in a non–cell-autonomous manner such that motoneurons are critical for the onset, and glia contribute to progression of the disease. Recently, it has been shown in Drosophila melanogaster that expression of human SOD1 in a subset of neuronal cells causes synaptic transmission defects, modified motor function, and altered sensitivity to compounds that induce oxidative stress. Here we used the Gal4-UAS (Upstream Activation Sequence) system to further characterize flies expressing wild-type Drosophila SOD1 (dSOD1) and the mutant human SOD1(G85R) (G85R) allele in motoneurons and glia. Cell-specific expression of both dSOD1 and G85R was found to influence lifespan, affect sensitivity to hydrogen peroxide, and alter lipid peroxidation levels. To better understand the genetic consequences of G85R expression in motoneurons and glia, we conducted microarray analysis of both young flies (5 days old) and old flies (45 days old) expressing G85R selectively in motoneurons or glia and concurrently in motoneurons and glia. Results from this microarray experiment identified candidate genes for further investigation and may help elucidate the individual and combined contributions of motoneurons and glia in ALS. Genetics Society of America 2013-04-01 /pmc/articles/PMC3618356/ /pubmed/23550139 http://dx.doi.org/10.1534/g3.113.005850 Text en Copyright © 2013 Kumimoto et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Investigations
Kumimoto, Emily L.
Fore, Taylor R.
Zhang, Bing
Transcriptome Profiling Following Neuronal and Glial Expression of ALS-Linked SOD1 in Drosophila
title Transcriptome Profiling Following Neuronal and Glial Expression of ALS-Linked SOD1 in Drosophila
title_full Transcriptome Profiling Following Neuronal and Glial Expression of ALS-Linked SOD1 in Drosophila
title_fullStr Transcriptome Profiling Following Neuronal and Glial Expression of ALS-Linked SOD1 in Drosophila
title_full_unstemmed Transcriptome Profiling Following Neuronal and Glial Expression of ALS-Linked SOD1 in Drosophila
title_short Transcriptome Profiling Following Neuronal and Glial Expression of ALS-Linked SOD1 in Drosophila
title_sort transcriptome profiling following neuronal and glial expression of als-linked sod1 in drosophila
topic Investigations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3618356/
https://www.ncbi.nlm.nih.gov/pubmed/23550139
http://dx.doi.org/10.1534/g3.113.005850
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