In silico analysis of hub genes and regulatory networks implicates the putamen in non-motor Parkinson’s disease disorders
Abstract Background Parkinson’s disease (PD) is a neurodegenerative condition marked by the gradual degeneration of dopaminergic neurons in the substantia nigra, leading to depletion of the dopaminergic neurons in the substantia nigra as well as degeneration as and decreased activity in the putamen....
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SpringerOpen
2025-01-01
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| Series: | Egyptian Journal of Medical Human Genetics |
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| Online Access: | https://doi.org/10.1186/s43042-025-00643-5 |
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| author | Stephen Tunmise Akanbi Joshua Ayodele Yusuf Thompson Oluwaferanmi Ayandele Dayo Samson Oladipupo Darasimi Racheal Olorunlowu Blessing Dorcas Olawuyi Joshua Oluwafisayo Adepoju Dolapo Emmanuel Opasina Elizabeth Kehinde Opoola Uchenna Victor Ugwuanyi Olufunto Omodele Adeleye |
| author_facet | Stephen Tunmise Akanbi Joshua Ayodele Yusuf Thompson Oluwaferanmi Ayandele Dayo Samson Oladipupo Darasimi Racheal Olorunlowu Blessing Dorcas Olawuyi Joshua Oluwafisayo Adepoju Dolapo Emmanuel Opasina Elizabeth Kehinde Opoola Uchenna Victor Ugwuanyi Olufunto Omodele Adeleye |
| author_sort | Stephen Tunmise Akanbi |
| collection | DOAJ |
| description | Abstract Background Parkinson’s disease (PD) is a neurodegenerative condition marked by the gradual degeneration of dopaminergic neurons in the substantia nigra, leading to depletion of the dopaminergic neurons in the substantia nigra as well as degeneration as and decreased activity in the putamen. This study aims to identify the role of putamen in non-motor PD symptoms as well as potential therapeutic target in the putamen of PD. Methods Transcriptome profiles of PD (dataset number: GSE205450, obtained from postmortem putamen and caudate samples from forty controls and thirty-five PD patients) were retrieved from the Gene Expression Omnibus (GEO) database. Specifically, we focused on putamen data for controls and PD patients. Differential gene expression analysis was carried out using with Limma, filtering for genes with |logFC|> 1 (fold change) and p < 0.05 (p-value). Protein–Protein Interaction networks were constructed using stringDB (combined score > 0.7) and analyzed in Cytoscape to identify hub genes based on various topological measures (EPC, MCC, MNC, Degree, and EcCentricity). Enrichment analysis of target genes was conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Also, we constructed transcription factor (TF)-hub gene expression networks, miRNA-hub gene expression networks, and disease hub gene association networks using the JASPAR database, Tarbase database, and DisGeNET via NetworkAnalyst platform, respectively. Results Seven genes, namely SST, NPY, IL6, PVALB, ALB, NTS, and TH were identified as hub genes in PD putamen. Notable miRNAs included hsa-mir-34a-5p, hsa-mir-15a-5p, hsa-mir-424-5p, and hsa-mir-19b-3p, while key transcription factors include GATA2, CREB1, FOXC1, FOXL1, TID1, NFKB1, YY1, SPIB, GATA3, and STAT3. Conclusions Our findings revealed close associations between the hub genes of PD putamen and non-motor symptoms of PD such as major depressive disorder, mood disorders and schizophrenia. These findings may provide a new direction for developing therapy for non-motor symptoms of PD and wet lab research is encouraged. |
| format | Article |
| id | doaj-art-47bf84797c0046a08758e07d1e10cb58 |
| institution | Kabale University |
| issn | 2090-2441 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Egyptian Journal of Medical Human Genetics |
| spelling | doaj-art-47bf84797c0046a08758e07d1e10cb582025-01-26T12:36:43ZengSpringerOpenEgyptian Journal of Medical Human Genetics2090-24412025-01-0126111410.1186/s43042-025-00643-5In silico analysis of hub genes and regulatory networks implicates the putamen in non-motor Parkinson’s disease disordersStephen Tunmise Akanbi0Joshua Ayodele Yusuf1Thompson Oluwaferanmi Ayandele2Dayo Samson Oladipupo3Darasimi Racheal Olorunlowu4Blessing Dorcas Olawuyi5Joshua Oluwafisayo Adepoju6Dolapo Emmanuel Opasina7Elizabeth Kehinde Opoola8Uchenna Victor Ugwuanyi9Olufunto Omodele Adeleye10Central Research and Diagnostic LaboratoryNigerian Institute of Medical ResearchDepartment of Anatomy, Ladoke Akintola University of TechnologyDepartment of Anatomy, Ladoke Akintola University of TechnologyDepartment of Anatomy, Ladoke Akintola University of TechnologyDepartment of Physiology, Ladoke Akintola University of TechnologyDepartment of Anatomy, Ladoke Akintola University of TechnologyDepartment of Biochemistry, Ladoke Akintola University of TechnologyDepartment of Anatomy, Ladoke Akintola University of TechnologyDepartment of Chemistry, University of IlorinDepartment of Anatomy, Ladoke Akintola University of TechnologyAbstract Background Parkinson’s disease (PD) is a neurodegenerative condition marked by the gradual degeneration of dopaminergic neurons in the substantia nigra, leading to depletion of the dopaminergic neurons in the substantia nigra as well as degeneration as and decreased activity in the putamen. This study aims to identify the role of putamen in non-motor PD symptoms as well as potential therapeutic target in the putamen of PD. Methods Transcriptome profiles of PD (dataset number: GSE205450, obtained from postmortem putamen and caudate samples from forty controls and thirty-five PD patients) were retrieved from the Gene Expression Omnibus (GEO) database. Specifically, we focused on putamen data for controls and PD patients. Differential gene expression analysis was carried out using with Limma, filtering for genes with |logFC|> 1 (fold change) and p < 0.05 (p-value). Protein–Protein Interaction networks were constructed using stringDB (combined score > 0.7) and analyzed in Cytoscape to identify hub genes based on various topological measures (EPC, MCC, MNC, Degree, and EcCentricity). Enrichment analysis of target genes was conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Also, we constructed transcription factor (TF)-hub gene expression networks, miRNA-hub gene expression networks, and disease hub gene association networks using the JASPAR database, Tarbase database, and DisGeNET via NetworkAnalyst platform, respectively. Results Seven genes, namely SST, NPY, IL6, PVALB, ALB, NTS, and TH were identified as hub genes in PD putamen. Notable miRNAs included hsa-mir-34a-5p, hsa-mir-15a-5p, hsa-mir-424-5p, and hsa-mir-19b-3p, while key transcription factors include GATA2, CREB1, FOXC1, FOXL1, TID1, NFKB1, YY1, SPIB, GATA3, and STAT3. Conclusions Our findings revealed close associations between the hub genes of PD putamen and non-motor symptoms of PD such as major depressive disorder, mood disorders and schizophrenia. These findings may provide a new direction for developing therapy for non-motor symptoms of PD and wet lab research is encouraged.https://doi.org/10.1186/s43042-025-00643-5PutamenTranscriptomicsParkinson’s diseaseHub genes |
| spellingShingle | Stephen Tunmise Akanbi Joshua Ayodele Yusuf Thompson Oluwaferanmi Ayandele Dayo Samson Oladipupo Darasimi Racheal Olorunlowu Blessing Dorcas Olawuyi Joshua Oluwafisayo Adepoju Dolapo Emmanuel Opasina Elizabeth Kehinde Opoola Uchenna Victor Ugwuanyi Olufunto Omodele Adeleye In silico analysis of hub genes and regulatory networks implicates the putamen in non-motor Parkinson’s disease disorders Egyptian Journal of Medical Human Genetics Putamen Transcriptomics Parkinson’s disease Hub genes |
| title | In silico analysis of hub genes and regulatory networks implicates the putamen in non-motor Parkinson’s disease disorders |
| title_full | In silico analysis of hub genes and regulatory networks implicates the putamen in non-motor Parkinson’s disease disorders |
| title_fullStr | In silico analysis of hub genes and regulatory networks implicates the putamen in non-motor Parkinson’s disease disorders |
| title_full_unstemmed | In silico analysis of hub genes and regulatory networks implicates the putamen in non-motor Parkinson’s disease disorders |
| title_short | In silico analysis of hub genes and regulatory networks implicates the putamen in non-motor Parkinson’s disease disorders |
| title_sort | in silico analysis of hub genes and regulatory networks implicates the putamen in non motor parkinson s disease disorders |
| topic | Putamen Transcriptomics Parkinson’s disease Hub genes |
| url | https://doi.org/10.1186/s43042-025-00643-5 |
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