Systematic analysis of cuproptosis-related genes in immunological characterization and predictive drugs in Alzheimer’s disease
ObjectivesThis study aimed to make a systematic analysis of cuproptosis-related genes (CRGs) in immunological characterization and predictive drugs in Alzheimer’s disease (AD) through bioinformatics and biological experiments.MethodsThe molecular clusters related to CRGs and associated immune cell i...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2023.1204530/full |
| _version_ | 1797657466452836352 |
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| author | Bin Nie Bin Nie Yefen Duan Xuelong Xie Xuelong Xie Lihua Qiu Shaorui Shi Shaorui Shi Zhili Fan Zhili Fan Xuxiang Zheng Xuxiang Zheng Ling Jiang |
| author_facet | Bin Nie Bin Nie Yefen Duan Xuelong Xie Xuelong Xie Lihua Qiu Shaorui Shi Shaorui Shi Zhili Fan Zhili Fan Xuxiang Zheng Xuxiang Zheng Ling Jiang |
| author_sort | Bin Nie |
| collection | DOAJ |
| description | ObjectivesThis study aimed to make a systematic analysis of cuproptosis-related genes (CRGs) in immunological characterization and predictive drugs in Alzheimer’s disease (AD) through bioinformatics and biological experiments.MethodsThe molecular clusters related to CRGs and associated immune cell infiltrations in AD were investigated. The diagnostic models were constructed for AD and different AD subtypes. Moreover, drug prediction and molecular docking were also performed. Subsequently, a molecular dynamics (MD) simulation was conducted to further verify the findings. Finally, RT-qPCR validation was performed.ResultsThe characterization of 12 AD-related CRGs was evaluated in AD, and a diagnostic model for AD showed a satisfying discrimination power based on five CRGs by LASSO regression analysis. The dysregulated CRGs and activated immune responses partially differed between patients with AD and healthy subjects. Furthermore, two molecular subtypes (clusters A and B) with different immune infiltration characteristics in AD were identified. Similarly, a diagnostic model for different AD subtypes was built with nine CRGs, which achieved a good performance. Molecular docking revealed the optimum conformation of CHEMBL261454 and its target gene CSNK1D, which was further validated by MD simulation. The RT-qPCR results were consistent with those of the comprehensive analysis.ConclusionThis study systematically elucidated the complex relationship between cuproptosis and AD, providing novel molecular targets for treatment and diagnosis biomarkers of AD. |
| first_indexed | 2024-03-11T17:44:54Z |
| format | Article |
| id | doaj.art-786bc37693474742aca476ad8675354d |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-03-11T17:44:54Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-786bc37693474742aca476ad8675354d2023-10-18T08:22:41ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652023-10-011510.3389/fnagi.2023.12045301204530Systematic analysis of cuproptosis-related genes in immunological characterization and predictive drugs in Alzheimer’s diseaseBin Nie0Bin Nie1Yefen Duan2Xuelong Xie3Xuelong Xie4Lihua Qiu5Shaorui Shi6Shaorui Shi7Zhili Fan8Zhili Fan9Xuxiang Zheng10Xuxiang Zheng11Ling Jiang12Department of Clinical Laboratory, The Second People’s Hospital of Yibin·West China Yibin Hospital, Sichuan University, Yibin, ChinaClinical Research and Translational Center, The Second People’s Hospital of Yibin·West China Yibin Hospital, Sichuan University, Yibin, ChinaDepartment of Clinical Laboratory, Yibin No. 4 People’s Hospital, Yibin, ChinaDepartment of Clinical Laboratory, The Second People’s Hospital of Yibin·West China Yibin Hospital, Sichuan University, Yibin, ChinaClinical Research and Translational Center, The Second People’s Hospital of Yibin·West China Yibin Hospital, Sichuan University, Yibin, ChinaImaging Department, The Second People’s Hospital of Yibin·West China Yibin Hospital, Sichuan University, Yibin, ChinaDepartment of Clinical Laboratory, The Second People’s Hospital of Yibin·West China Yibin Hospital, Sichuan University, Yibin, ChinaClinical Research and Translational Center, The Second People’s Hospital of Yibin·West China Yibin Hospital, Sichuan University, Yibin, ChinaDepartment of Clinical Laboratory, The Second People’s Hospital of Yibin·West China Yibin Hospital, Sichuan University, Yibin, ChinaClinical Research and Translational Center, The Second People’s Hospital of Yibin·West China Yibin Hospital, Sichuan University, Yibin, ChinaDepartment of Clinical Laboratory, The Second People’s Hospital of Yibin·West China Yibin Hospital, Sichuan University, Yibin, ChinaClinical Research and Translational Center, The Second People’s Hospital of Yibin·West China Yibin Hospital, Sichuan University, Yibin, ChinaDepartment of Neurology, The Second People’s Hospital of Yibin·West China Yibin Hospital, Sichuan University, Yibin, ChinaObjectivesThis study aimed to make a systematic analysis of cuproptosis-related genes (CRGs) in immunological characterization and predictive drugs in Alzheimer’s disease (AD) through bioinformatics and biological experiments.MethodsThe molecular clusters related to CRGs and associated immune cell infiltrations in AD were investigated. The diagnostic models were constructed for AD and different AD subtypes. Moreover, drug prediction and molecular docking were also performed. Subsequently, a molecular dynamics (MD) simulation was conducted to further verify the findings. Finally, RT-qPCR validation was performed.ResultsThe characterization of 12 AD-related CRGs was evaluated in AD, and a diagnostic model for AD showed a satisfying discrimination power based on five CRGs by LASSO regression analysis. The dysregulated CRGs and activated immune responses partially differed between patients with AD and healthy subjects. Furthermore, two molecular subtypes (clusters A and B) with different immune infiltration characteristics in AD were identified. Similarly, a diagnostic model for different AD subtypes was built with nine CRGs, which achieved a good performance. Molecular docking revealed the optimum conformation of CHEMBL261454 and its target gene CSNK1D, which was further validated by MD simulation. The RT-qPCR results were consistent with those of the comprehensive analysis.ConclusionThis study systematically elucidated the complex relationship between cuproptosis and AD, providing novel molecular targets for treatment and diagnosis biomarkers of AD.https://www.frontiersin.org/articles/10.3389/fnagi.2023.1204530/fullAlzheimer’s diseasecuproptosisimmune microenvironmentdiagnostic modelmolecular docking |
| spellingShingle | Bin Nie Bin Nie Yefen Duan Xuelong Xie Xuelong Xie Lihua Qiu Shaorui Shi Shaorui Shi Zhili Fan Zhili Fan Xuxiang Zheng Xuxiang Zheng Ling Jiang Systematic analysis of cuproptosis-related genes in immunological characterization and predictive drugs in Alzheimer’s disease Frontiers in Aging Neuroscience Alzheimer’s disease cuproptosis immune microenvironment diagnostic model molecular docking |
| title | Systematic analysis of cuproptosis-related genes in immunological characterization and predictive drugs in Alzheimer’s disease |
| title_full | Systematic analysis of cuproptosis-related genes in immunological characterization and predictive drugs in Alzheimer’s disease |
| title_fullStr | Systematic analysis of cuproptosis-related genes in immunological characterization and predictive drugs in Alzheimer’s disease |
| title_full_unstemmed | Systematic analysis of cuproptosis-related genes in immunological characterization and predictive drugs in Alzheimer’s disease |
| title_short | Systematic analysis of cuproptosis-related genes in immunological characterization and predictive drugs in Alzheimer’s disease |
| title_sort | systematic analysis of cuproptosis related genes in immunological characterization and predictive drugs in alzheimer s disease |
| topic | Alzheimer’s disease cuproptosis immune microenvironment diagnostic model molecular docking |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2023.1204530/full |
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