Bioinformatic Analysis Reveals Phosphodiesterase 4D-Interacting Protein as a Key Frontal Cortex Dementia Switch Gene
The mechanisms that initiate dementia are poorly understood and there are currently no treatments that can slow their progression. The identification of key genes and molecular pathways that may trigger dementia should help reveal potential therapeutic reagents. In this study, SWItch Miner software...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/11/3787 |
| _version_ | 1797566857637527552 |
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| author | Judith A. Potashkin Virginie Bottero Jose A. Santiago James P. Quinn |
| author_facet | Judith A. Potashkin Virginie Bottero Jose A. Santiago James P. Quinn |
| author_sort | Judith A. Potashkin |
| collection | DOAJ |
| description | The mechanisms that initiate dementia are poorly understood and there are currently no treatments that can slow their progression. The identification of key genes and molecular pathways that may trigger dementia should help reveal potential therapeutic reagents. In this study, SWItch Miner software was used to identify phosphodiesterase 4D-interacting protein as a key factor that may lead to the development of Alzheimer’s disease, vascular dementia, and frontotemporal dementia. Inflammation, PI3K-AKT, and ubiquitin-mediated proteolysis were identified as the main pathways that are dysregulated in these dementias. All of these dementias are regulated by 12 shared transcription factors. Protein–chemical interaction network analysis of dementia switch genes revealed that valproic acid may be neuroprotective for these dementias. Collectively, we identified shared and unique dysregulated gene expression, pathways and regulatory factors among dementias. New key mechanisms that lead to the development of dementia were revealed and it is expected that these data will advance personalized medicine for patients. |
| first_indexed | 2024-03-10T19:33:19Z |
| format | Article |
| id | doaj.art-0978ae708469420fa9e3e172b6e4b5e6 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T19:33:19Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0978ae708469420fa9e3e172b6e4b5e62023-11-20T01:54:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-05-012111378710.3390/ijms21113787Bioinformatic Analysis Reveals Phosphodiesterase 4D-Interacting Protein as a Key Frontal Cortex Dementia Switch GeneJudith A. Potashkin0Virginie Bottero1Jose A. Santiago2James P. Quinn3Center for Neurodegenerative Diseases and Therapeutics, Cellular and Molecular Pharmacology Department, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USACenter for Neurodegenerative Diseases and Therapeutics, Cellular and Molecular Pharmacology Department, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USANeuroHub Analytics, LLC, Chicago, IL 60605, USAQ Regulating Systems, LLC, Gurnee, IL 60031, USAThe mechanisms that initiate dementia are poorly understood and there are currently no treatments that can slow their progression. The identification of key genes and molecular pathways that may trigger dementia should help reveal potential therapeutic reagents. In this study, SWItch Miner software was used to identify phosphodiesterase 4D-interacting protein as a key factor that may lead to the development of Alzheimer’s disease, vascular dementia, and frontotemporal dementia. Inflammation, PI3K-AKT, and ubiquitin-mediated proteolysis were identified as the main pathways that are dysregulated in these dementias. All of these dementias are regulated by 12 shared transcription factors. Protein–chemical interaction network analysis of dementia switch genes revealed that valproic acid may be neuroprotective for these dementias. Collectively, we identified shared and unique dysregulated gene expression, pathways and regulatory factors among dementias. New key mechanisms that lead to the development of dementia were revealed and it is expected that these data will advance personalized medicine for patients.https://www.mdpi.com/1422-0067/21/11/3787dementiaAlzheimer’s diseasevascular dementiafrontotemporal dementiaswitch genesphosphodiesterase 4D-interacting protein |
| spellingShingle | Judith A. Potashkin Virginie Bottero Jose A. Santiago James P. Quinn Bioinformatic Analysis Reveals Phosphodiesterase 4D-Interacting Protein as a Key Frontal Cortex Dementia Switch Gene International Journal of Molecular Sciences dementia Alzheimer’s disease vascular dementia frontotemporal dementia switch genes phosphodiesterase 4D-interacting protein |
| title | Bioinformatic Analysis Reveals Phosphodiesterase 4D-Interacting Protein as a Key Frontal Cortex Dementia Switch Gene |
| title_full | Bioinformatic Analysis Reveals Phosphodiesterase 4D-Interacting Protein as a Key Frontal Cortex Dementia Switch Gene |
| title_fullStr | Bioinformatic Analysis Reveals Phosphodiesterase 4D-Interacting Protein as a Key Frontal Cortex Dementia Switch Gene |
| title_full_unstemmed | Bioinformatic Analysis Reveals Phosphodiesterase 4D-Interacting Protein as a Key Frontal Cortex Dementia Switch Gene |
| title_short | Bioinformatic Analysis Reveals Phosphodiesterase 4D-Interacting Protein as a Key Frontal Cortex Dementia Switch Gene |
| title_sort | bioinformatic analysis reveals phosphodiesterase 4d interacting protein as a key frontal cortex dementia switch gene |
| topic | dementia Alzheimer’s disease vascular dementia frontotemporal dementia switch genes phosphodiesterase 4D-interacting protein |
| url | https://www.mdpi.com/1422-0067/21/11/3787 |
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