The Role of Superoxide Dismutase 1 in Amyotrophic Lateral Sclerosis: Identification of Signaling Pathways, Regulators, Molecular Interaction Networks, and Biological Functions through Bioinformatics
Mutations in superoxide dismutase 1 (SOD1) result in misfolding and aggregation of the protein, causing neurodegenerative amyotrophic lateral sclerosis (ALS). In recent years, several new SOD1 variants that trigger ALS have been identified, making it increasingly crucial to understand the SOD1 toxic...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/13/1/151 |
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| author | Sharad Kumar Suthar Sang-Yoon Lee |
| author_facet | Sharad Kumar Suthar Sang-Yoon Lee |
| author_sort | Sharad Kumar Suthar |
| collection | DOAJ |
| description | Mutations in superoxide dismutase 1 (SOD1) result in misfolding and aggregation of the protein, causing neurodegenerative amyotrophic lateral sclerosis (ALS). In recent years, several new SOD1 variants that trigger ALS have been identified, making it increasingly crucial to understand the SOD1 toxicity pathway in ALS. Here we used an integrated bioinformatics approach, including the Ingenuity Pathway Analysis (IPA) tool to analyze signaling pathways, regulators, functions, and network molecules of SOD1 with an emphasis on ALS. IPA toxicity analysis of SOD1 identified superoxide radicals’ degradation, apelin adipocyte, ALS, NRF2-mediated oxidative stress response, and sirtuin signaling as the key signaling pathways, while the toxicity of SOD1 is exerted via mitochondrial swelling and oxidative stress. IPA listed CNR1, APLN, BTG2, MAPK, DRAP1, NFE2L2, SNCA, and CG as the upstream regulators of SOD1. IPA further revealed that mutation in SOD1 results in hereditary disorders, including ALS. The exploration of the relationship between SOD1 and ALS using IPA unveiled SOD1-ALS pathway molecules. The gene ontology (GO) analysis of SOD1-ALS pathway molecules with ShinyGO reaffirmed that SOD1 toxicity results in ALS and neurodegeneration. The GO analysis further identified enriched biological processes, molecular functions, and cellular components for SOD1-ALS pathway molecules. The construction of a protein–protein interaction network of SOD1-ALS pathway molecules using STRING and further analysis of that network with Cytoscape identified ACTB followed by TP53, IL6, CASP3, SOD1, IL1B, APP, APOE, and VEGFA as the major network hubs. Taken together, our study provides insight into the molecular underpinning of SOD1’s toxicity in ALS. |
| first_indexed | 2024-03-09T13:22:33Z |
| format | Article |
| id | doaj.art-99bff9e00b704cb38a6059b99e8a04b4 |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-09T13:22:33Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-99bff9e00b704cb38a6059b99e8a04b42023-11-30T21:28:23ZengMDPI AGBrain Sciences2076-34252023-01-0113115110.3390/brainsci13010151The Role of Superoxide Dismutase 1 in Amyotrophic Lateral Sclerosis: Identification of Signaling Pathways, Regulators, Molecular Interaction Networks, and Biological Functions through BioinformaticsSharad Kumar Suthar0Sang-Yoon Lee1Neuroscience Research Institute, Gachon University, Incheon 21565, Republic of KoreaNeuroscience Research Institute, Gachon University, Incheon 21565, Republic of KoreaMutations in superoxide dismutase 1 (SOD1) result in misfolding and aggregation of the protein, causing neurodegenerative amyotrophic lateral sclerosis (ALS). In recent years, several new SOD1 variants that trigger ALS have been identified, making it increasingly crucial to understand the SOD1 toxicity pathway in ALS. Here we used an integrated bioinformatics approach, including the Ingenuity Pathway Analysis (IPA) tool to analyze signaling pathways, regulators, functions, and network molecules of SOD1 with an emphasis on ALS. IPA toxicity analysis of SOD1 identified superoxide radicals’ degradation, apelin adipocyte, ALS, NRF2-mediated oxidative stress response, and sirtuin signaling as the key signaling pathways, while the toxicity of SOD1 is exerted via mitochondrial swelling and oxidative stress. IPA listed CNR1, APLN, BTG2, MAPK, DRAP1, NFE2L2, SNCA, and CG as the upstream regulators of SOD1. IPA further revealed that mutation in SOD1 results in hereditary disorders, including ALS. The exploration of the relationship between SOD1 and ALS using IPA unveiled SOD1-ALS pathway molecules. The gene ontology (GO) analysis of SOD1-ALS pathway molecules with ShinyGO reaffirmed that SOD1 toxicity results in ALS and neurodegeneration. The GO analysis further identified enriched biological processes, molecular functions, and cellular components for SOD1-ALS pathway molecules. The construction of a protein–protein interaction network of SOD1-ALS pathway molecules using STRING and further analysis of that network with Cytoscape identified ACTB followed by TP53, IL6, CASP3, SOD1, IL1B, APP, APOE, and VEGFA as the major network hubs. Taken together, our study provides insight into the molecular underpinning of SOD1’s toxicity in ALS.https://www.mdpi.com/2076-3425/13/1/151superoxide dismutase 1antioxidantamyotrophic lateral sclerosiscanonical pathwaysregulatorsmolecular interaction network |
| spellingShingle | Sharad Kumar Suthar Sang-Yoon Lee The Role of Superoxide Dismutase 1 in Amyotrophic Lateral Sclerosis: Identification of Signaling Pathways, Regulators, Molecular Interaction Networks, and Biological Functions through Bioinformatics Brain Sciences superoxide dismutase 1 antioxidant amyotrophic lateral sclerosis canonical pathways regulators molecular interaction network |
| title | The Role of Superoxide Dismutase 1 in Amyotrophic Lateral Sclerosis: Identification of Signaling Pathways, Regulators, Molecular Interaction Networks, and Biological Functions through Bioinformatics |
| title_full | The Role of Superoxide Dismutase 1 in Amyotrophic Lateral Sclerosis: Identification of Signaling Pathways, Regulators, Molecular Interaction Networks, and Biological Functions through Bioinformatics |
| title_fullStr | The Role of Superoxide Dismutase 1 in Amyotrophic Lateral Sclerosis: Identification of Signaling Pathways, Regulators, Molecular Interaction Networks, and Biological Functions through Bioinformatics |
| title_full_unstemmed | The Role of Superoxide Dismutase 1 in Amyotrophic Lateral Sclerosis: Identification of Signaling Pathways, Regulators, Molecular Interaction Networks, and Biological Functions through Bioinformatics |
| title_short | The Role of Superoxide Dismutase 1 in Amyotrophic Lateral Sclerosis: Identification of Signaling Pathways, Regulators, Molecular Interaction Networks, and Biological Functions through Bioinformatics |
| title_sort | role of superoxide dismutase 1 in amyotrophic lateral sclerosis identification of signaling pathways regulators molecular interaction networks and biological functions through bioinformatics |
| topic | superoxide dismutase 1 antioxidant amyotrophic lateral sclerosis canonical pathways regulators molecular interaction network |
| url | https://www.mdpi.com/2076-3425/13/1/151 |
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