Dysregulations of Expression of Genes of the Ubiquitin/SUMO Pathways in an In Vitro Model of Amyotrophic Lateral Sclerosis Combining Oxidative Stress and SOD1 Gene Mutation
Protein aggregates in affected motor neurons are a hallmark of amyotrophic lateral sclerosis (ALS), but the molecular pathways leading to their formation remain incompletely understood. Oxidative stress associated with age, the major risk factor in ALS, contributes to this neurodegeneration in ALS....
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| Format: | Article |
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/4/1796 |
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| author | Audrey Dangoumau Sylviane Marouillat Roxane Coelho François Wurmser Céline Brulard Shanez Haouari Frédéric Laumonnier Philippe Corcia Christian R. Andres Hélène Blasco Patrick Vourc’h |
| author_facet | Audrey Dangoumau Sylviane Marouillat Roxane Coelho François Wurmser Céline Brulard Shanez Haouari Frédéric Laumonnier Philippe Corcia Christian R. Andres Hélène Blasco Patrick Vourc’h |
| author_sort | Audrey Dangoumau |
| collection | DOAJ |
| description | Protein aggregates in affected motor neurons are a hallmark of amyotrophic lateral sclerosis (ALS), but the molecular pathways leading to their formation remain incompletely understood. Oxidative stress associated with age, the major risk factor in ALS, contributes to this neurodegeneration in ALS. We show that several genes coding for enzymes of the ubiquitin and small ubiquitin-related modifier (SUMO) pathways exhibit altered expression in motor neuronal cells exposed to oxidative stress, such as the CCNF gene mutated in ALS patients. Eleven of these genes were further studied in conditions combining oxidative stress and the expression of an ALS related mutant of the superoxide dismutase 1 (SOD1) gene. We observed a combined effect of these two environmental and genetic factors on the expression of genes, such as Uhrf2, Rbx1, Kdm2b, Ube2d2, Xaf1, and Senp1. Overall, we identified dysregulations in the expression of enzymes of the ubiquitin and SUMO pathways that may be of interest to better understand the pathophysiology of ALS and to protect motor neurons from oxidative stress and genetic alterations. |
| first_indexed | 2024-03-09T00:57:26Z |
| format | Article |
| id | doaj.art-391178bd96564bfaa3a5e9dd414272cd |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T00:57:26Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-391178bd96564bfaa3a5e9dd414272cd2023-12-11T16:46:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224179610.3390/ijms22041796Dysregulations of Expression of Genes of the Ubiquitin/SUMO Pathways in an In Vitro Model of Amyotrophic Lateral Sclerosis Combining Oxidative Stress and SOD1 Gene MutationAudrey Dangoumau0Sylviane Marouillat1Roxane Coelho2François Wurmser3Céline Brulard4Shanez Haouari5Frédéric Laumonnier6Philippe Corcia7Christian R. Andres8Hélène Blasco9Patrick Vourc’h10UMR iBrain, Université de Tours, Inserm, 37000 Tours, FranceUMR iBrain, Université de Tours, Inserm, 37000 Tours, FranceUMR iBrain, Université de Tours, Inserm, 37000 Tours, FranceUMR iBrain, Université de Tours, Inserm, 37000 Tours, FranceUTTIL, CHRU de Tours, 37000 Tours, FranceUMR iBrain, Université de Tours, Inserm, 37000 Tours, FranceUMR iBrain, Université de Tours, Inserm, 37000 Tours, FranceUMR iBrain, Université de Tours, Inserm, 37000 Tours, FranceUMR iBrain, Université de Tours, Inserm, 37000 Tours, FranceUMR iBrain, Université de Tours, Inserm, 37000 Tours, FranceUMR iBrain, Université de Tours, Inserm, 37000 Tours, FranceProtein aggregates in affected motor neurons are a hallmark of amyotrophic lateral sclerosis (ALS), but the molecular pathways leading to their formation remain incompletely understood. Oxidative stress associated with age, the major risk factor in ALS, contributes to this neurodegeneration in ALS. We show that several genes coding for enzymes of the ubiquitin and small ubiquitin-related modifier (SUMO) pathways exhibit altered expression in motor neuronal cells exposed to oxidative stress, such as the CCNF gene mutated in ALS patients. Eleven of these genes were further studied in conditions combining oxidative stress and the expression of an ALS related mutant of the superoxide dismutase 1 (SOD1) gene. We observed a combined effect of these two environmental and genetic factors on the expression of genes, such as Uhrf2, Rbx1, Kdm2b, Ube2d2, Xaf1, and Senp1. Overall, we identified dysregulations in the expression of enzymes of the ubiquitin and SUMO pathways that may be of interest to better understand the pathophysiology of ALS and to protect motor neurons from oxidative stress and genetic alterations.https://www.mdpi.com/1422-0067/22/4/1796ALSubiquitinSUMOSOD1oxidative stress |
| spellingShingle | Audrey Dangoumau Sylviane Marouillat Roxane Coelho François Wurmser Céline Brulard Shanez Haouari Frédéric Laumonnier Philippe Corcia Christian R. Andres Hélène Blasco Patrick Vourc’h Dysregulations of Expression of Genes of the Ubiquitin/SUMO Pathways in an In Vitro Model of Amyotrophic Lateral Sclerosis Combining Oxidative Stress and SOD1 Gene Mutation International Journal of Molecular Sciences ALS ubiquitin SUMO SOD1 oxidative stress |
| title | Dysregulations of Expression of Genes of the Ubiquitin/SUMO Pathways in an In Vitro Model of Amyotrophic Lateral Sclerosis Combining Oxidative Stress and SOD1 Gene Mutation |
| title_full | Dysregulations of Expression of Genes of the Ubiquitin/SUMO Pathways in an In Vitro Model of Amyotrophic Lateral Sclerosis Combining Oxidative Stress and SOD1 Gene Mutation |
| title_fullStr | Dysregulations of Expression of Genes of the Ubiquitin/SUMO Pathways in an In Vitro Model of Amyotrophic Lateral Sclerosis Combining Oxidative Stress and SOD1 Gene Mutation |
| title_full_unstemmed | Dysregulations of Expression of Genes of the Ubiquitin/SUMO Pathways in an In Vitro Model of Amyotrophic Lateral Sclerosis Combining Oxidative Stress and SOD1 Gene Mutation |
| title_short | Dysregulations of Expression of Genes of the Ubiquitin/SUMO Pathways in an In Vitro Model of Amyotrophic Lateral Sclerosis Combining Oxidative Stress and SOD1 Gene Mutation |
| title_sort | dysregulations of expression of genes of the ubiquitin sumo pathways in an in vitro model of amyotrophic lateral sclerosis combining oxidative stress and sod1 gene mutation |
| topic | ALS ubiquitin SUMO SOD1 oxidative stress |
| url | https://www.mdpi.com/1422-0067/22/4/1796 |
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