Unveiling ferroptosis genes and inhibitors in diabetic retinopathy through single-cell analysis and docking simulations
Diabetic retinopathy (DR) is a common microvascular complication of diabetes and a leading cause of vision loss worldwide. Although several mechanisms have been implicated in the pathogenesis of DR, emerging evidence suggests a link between ferroptosis and DR. Unfortunately, the exact mechanism unde...
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Elsevier
2025-03-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580825000196 |
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| author | Md. Maqsood Ahamad Khan Ananya Ganguly Shubhrajit Barman Chirasmita Das Senthil Kumar Ganesan |
| author_facet | Md. Maqsood Ahamad Khan Ananya Ganguly Shubhrajit Barman Chirasmita Das Senthil Kumar Ganesan |
| author_sort | Md. Maqsood Ahamad Khan |
| collection | DOAJ |
| description | Diabetic retinopathy (DR) is a common microvascular complication of diabetes and a leading cause of vision loss worldwide. Although several mechanisms have been implicated in the pathogenesis of DR, emerging evidence suggests a link between ferroptosis and DR. Unfortunately, the exact mechanism underlying this connection is not clear. Therefore, investigating the role of ferroptosis in diabetic retinopathy holds promise for advancing our understanding of this complex disease and developing innovative treatments. We have identified differentially expressed genes (DEGs) and differentially expressed marker genes (DEMGs) from open-source single-cell RNA sequencing datasets by using in depth in silico approach. Subsequently, ferroptosis-associated DEGs (FA-DEGs), ferroptosis-associated DEMGs (FA-DEMGs), and ferroptosis-associated Hub Genes (FAHGs) were identified. The FDA-approved drugs for our target proteins were also identified, and their ADMET properties were assessed. Molecular docking and simulation were utilized to explore the interaction stability of the compounds with the target proteins. Overall, we identified 63 FA-DEMGs that were significantly enriched in Peroxiredoxin activity, Ferroptosis, Mitophagy, and Autophagy. Further analysis predicted that PRDX1 and UBC are candidate target proteins. Molecular docking results showed that dexamethasone has a high binding affinity for both PRDX1 and UBC. Additionally, molecular dynamics simulations revealed that dexamethasone (which showed the best hit in the docking analysis) exhibited a ‘stable effect’ on both PRDX1 and UBC. To summarize, this study showed that PRDX1 and UBC could be suitable therapeutic targets for dexamethasone, which might be helpful in the advance of DR treatments in the future. |
| format | Article |
| id | doaj-art-a0feef083daa436884dbd464948205cd |
| institution | DOAJ |
| issn | 2405-5808 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj-art-a0feef083daa436884dbd464948205cd2025-08-20T02:46:29ZengElsevierBiochemistry and Biophysics Reports2405-58082025-03-014110193210.1016/j.bbrep.2025.101932Unveiling ferroptosis genes and inhibitors in diabetic retinopathy through single-cell analysis and docking simulationsMd. Maqsood Ahamad Khan0Ananya Ganguly1Shubhrajit Barman2Chirasmita Das3Senthil Kumar Ganesan4Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata, 700032, India; CSIR-Indian Institute of Chemical Biology, Translational Research Unit of Excellence (TRUE), Kolkata, 700091, IndiaStructural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata, 700032, India; CSIR-Indian Institute of Chemical Biology, Translational Research Unit of Excellence (TRUE), Kolkata, 700091, IndiaStructural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata, 700032, India; CSIR-Indian Institute of Chemical Biology, Translational Research Unit of Excellence (TRUE), Kolkata, 700091, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201 002, IndiaStructural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata, 700032, India; CSIR-Indian Institute of Chemical Biology, Translational Research Unit of Excellence (TRUE), Kolkata, 700091, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201 002, IndiaStructural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata, 700032, India; CSIR-Indian Institute of Chemical Biology, Translational Research Unit of Excellence (TRUE), Kolkata, 700091, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201 002, India; Corresponding author. Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata, 700032, India.Diabetic retinopathy (DR) is a common microvascular complication of diabetes and a leading cause of vision loss worldwide. Although several mechanisms have been implicated in the pathogenesis of DR, emerging evidence suggests a link between ferroptosis and DR. Unfortunately, the exact mechanism underlying this connection is not clear. Therefore, investigating the role of ferroptosis in diabetic retinopathy holds promise for advancing our understanding of this complex disease and developing innovative treatments. We have identified differentially expressed genes (DEGs) and differentially expressed marker genes (DEMGs) from open-source single-cell RNA sequencing datasets by using in depth in silico approach. Subsequently, ferroptosis-associated DEGs (FA-DEGs), ferroptosis-associated DEMGs (FA-DEMGs), and ferroptosis-associated Hub Genes (FAHGs) were identified. The FDA-approved drugs for our target proteins were also identified, and their ADMET properties were assessed. Molecular docking and simulation were utilized to explore the interaction stability of the compounds with the target proteins. Overall, we identified 63 FA-DEMGs that were significantly enriched in Peroxiredoxin activity, Ferroptosis, Mitophagy, and Autophagy. Further analysis predicted that PRDX1 and UBC are candidate target proteins. Molecular docking results showed that dexamethasone has a high binding affinity for both PRDX1 and UBC. Additionally, molecular dynamics simulations revealed that dexamethasone (which showed the best hit in the docking analysis) exhibited a ‘stable effect’ on both PRDX1 and UBC. To summarize, this study showed that PRDX1 and UBC could be suitable therapeutic targets for dexamethasone, which might be helpful in the advance of DR treatments in the future.http://www.sciencedirect.com/science/article/pii/S2405580825000196Diabetic retinopathyFerroptosisFerroptosis associated differentially expressed markers genesMolecular dockingMolecular dynamics simulationsTherapeutic targets |
| spellingShingle | Md. Maqsood Ahamad Khan Ananya Ganguly Shubhrajit Barman Chirasmita Das Senthil Kumar Ganesan Unveiling ferroptosis genes and inhibitors in diabetic retinopathy through single-cell analysis and docking simulations Biochemistry and Biophysics Reports Diabetic retinopathy Ferroptosis Ferroptosis associated differentially expressed markers genes Molecular docking Molecular dynamics simulations Therapeutic targets |
| title | Unveiling ferroptosis genes and inhibitors in diabetic retinopathy through single-cell analysis and docking simulations |
| title_full | Unveiling ferroptosis genes and inhibitors in diabetic retinopathy through single-cell analysis and docking simulations |
| title_fullStr | Unveiling ferroptosis genes and inhibitors in diabetic retinopathy through single-cell analysis and docking simulations |
| title_full_unstemmed | Unveiling ferroptosis genes and inhibitors in diabetic retinopathy through single-cell analysis and docking simulations |
| title_short | Unveiling ferroptosis genes and inhibitors in diabetic retinopathy through single-cell analysis and docking simulations |
| title_sort | unveiling ferroptosis genes and inhibitors in diabetic retinopathy through single cell analysis and docking simulations |
| topic | Diabetic retinopathy Ferroptosis Ferroptosis associated differentially expressed markers genes Molecular docking Molecular dynamics simulations Therapeutic targets |
| url | http://www.sciencedirect.com/science/article/pii/S2405580825000196 |
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