Investigating Pathogenetic Mechanisms of Alzheimer’s Disease by Systems Biology Approaches for Drug Discovery
Alzheimer’s disease (AD) is the most common cause of dementia, characterized by progressive cognitive decline and neurodegenerative disorder. Abnormal aggregations of intracellular neurofibrillary tangles (NFTs) and unusual accumulations of extracellular amyloid-β (Aβ) peptides are two important pat...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/20/11280 |
| _version_ | 1797514294195126272 |
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| author | Shan-Ju Yeh Ming-Hsun Chung Bor-Sen Chen |
| author_facet | Shan-Ju Yeh Ming-Hsun Chung Bor-Sen Chen |
| author_sort | Shan-Ju Yeh |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is the most common cause of dementia, characterized by progressive cognitive decline and neurodegenerative disorder. Abnormal aggregations of intracellular neurofibrillary tangles (NFTs) and unusual accumulations of extracellular amyloid-β (Aβ) peptides are two important pathological features in AD brains. However, in spite of large-scale clinical studies and computational simulations, the molecular mechanisms of AD development and progression are still unclear. In this study, we divided all of the samples into two groups: early stage (Braak score I–III) and later stage (Braak score IV–VI). By big database mining, the candidate genetic and epigenetic networks (GEN) have been constructed. In order to find out the real GENs for two stages of AD, we performed systems identification and system order detection scheme to prune false positives with the help of corresponding microarray data. Applying the principal network projection (PNP) method, core GENs were extracted from real GENs based on the projection values. By the annotation of KEGG pathway, we could obtain core pathways from core GENs and investigate pathogenetic mechanisms for the early and later stage of AD, respectively. Consequently, according to pathogenetic mechanisms, several potential biomarkers are identified as drug targets for multiple-molecule drug design in the treatment of AD. |
| first_indexed | 2024-03-10T06:29:44Z |
| format | Article |
| id | doaj.art-57ff41cb53ba46db83bc188003574816 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:29:44Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-57ff41cb53ba46db83bc1880035748162023-11-22T18:36:56ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122201128010.3390/ijms222011280Investigating Pathogenetic Mechanisms of Alzheimer’s Disease by Systems Biology Approaches for Drug DiscoveryShan-Ju Yeh0Ming-Hsun Chung1Bor-Sen Chen2Laboratory of Automatic Control, Signal Processing and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, TaiwanLaboratory of Automatic Control, Signal Processing and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, TaiwanLaboratory of Automatic Control, Signal Processing and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, TaiwanAlzheimer’s disease (AD) is the most common cause of dementia, characterized by progressive cognitive decline and neurodegenerative disorder. Abnormal aggregations of intracellular neurofibrillary tangles (NFTs) and unusual accumulations of extracellular amyloid-β (Aβ) peptides are two important pathological features in AD brains. However, in spite of large-scale clinical studies and computational simulations, the molecular mechanisms of AD development and progression are still unclear. In this study, we divided all of the samples into two groups: early stage (Braak score I–III) and later stage (Braak score IV–VI). By big database mining, the candidate genetic and epigenetic networks (GEN) have been constructed. In order to find out the real GENs for two stages of AD, we performed systems identification and system order detection scheme to prune false positives with the help of corresponding microarray data. Applying the principal network projection (PNP) method, core GENs were extracted from real GENs based on the projection values. By the annotation of KEGG pathway, we could obtain core pathways from core GENs and investigate pathogenetic mechanisms for the early and later stage of AD, respectively. Consequently, according to pathogenetic mechanisms, several potential biomarkers are identified as drug targets for multiple-molecule drug design in the treatment of AD.https://www.mdpi.com/1422-0067/22/20/11280Alzheimer’s diseasegenetic and epigenetic networkssystems biologydrug discovery |
| spellingShingle | Shan-Ju Yeh Ming-Hsun Chung Bor-Sen Chen Investigating Pathogenetic Mechanisms of Alzheimer’s Disease by Systems Biology Approaches for Drug Discovery International Journal of Molecular Sciences Alzheimer’s disease genetic and epigenetic networks systems biology drug discovery |
| title | Investigating Pathogenetic Mechanisms of Alzheimer’s Disease by Systems Biology Approaches for Drug Discovery |
| title_full | Investigating Pathogenetic Mechanisms of Alzheimer’s Disease by Systems Biology Approaches for Drug Discovery |
| title_fullStr | Investigating Pathogenetic Mechanisms of Alzheimer’s Disease by Systems Biology Approaches for Drug Discovery |
| title_full_unstemmed | Investigating Pathogenetic Mechanisms of Alzheimer’s Disease by Systems Biology Approaches for Drug Discovery |
| title_short | Investigating Pathogenetic Mechanisms of Alzheimer’s Disease by Systems Biology Approaches for Drug Discovery |
| title_sort | investigating pathogenetic mechanisms of alzheimer s disease by systems biology approaches for drug discovery |
| topic | Alzheimer’s disease genetic and epigenetic networks systems biology drug discovery |
| url | https://www.mdpi.com/1422-0067/22/20/11280 |
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