Preliminary In Vitro and In Vivo Insights of In Silico Candidate Repurposed Drugs for Alzheimer’s Disease
Alzheimer’s disease (AD) is a progressive neurodegenerative disease and is the most common type of dementia. Although a considerably large amount of money has been invested in drug development for AD, no disease modifying treatment has been detected so far. In our previous work, we developed a compu...
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MDPI AG
2023-04-01
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| Online Access: | https://www.mdpi.com/2075-1729/13/5/1095 |
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| author | Kyriaki Savva Margarita Zachariou Demos Kynigopoulos Eleni Fella Maria-Ioanna Vitali Xeni Kosofidou Michail Spyrou Irene Sargiannidou Elena Panayiotou Nikolas Dietis George M. Spyrou |
| author_facet | Kyriaki Savva Margarita Zachariou Demos Kynigopoulos Eleni Fella Maria-Ioanna Vitali Xeni Kosofidou Michail Spyrou Irene Sargiannidou Elena Panayiotou Nikolas Dietis George M. Spyrou |
| author_sort | Kyriaki Savva |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is a progressive neurodegenerative disease and is the most common type of dementia. Although a considerably large amount of money has been invested in drug development for AD, no disease modifying treatment has been detected so far. In our previous work, we developed a computational method to highlight stage-specific candidate repurposed drugs against AD. In this study, we tested the effect of the top 13 candidate repurposed drugs that we proposed in our previous work in a severity stage-specific manner using an in vitro BACE1 assay and the effect of a top-ranked drug from the list of our previous work, tetrabenazine (TBZ), in the 5XFAD as an AD mouse model. From our in vitro screening, we detected 2 compounds (clomiphene citrate and Pik-90) that showed statistically significant inhibition against the activity of the BACE1 enzyme. The administration of TBZ at the selected dose and therapeutic regimen in 5XFAD in male and female mice showed no significant effect in behavioral tests using the Y-maze and the ELISA immunoassay of Aβ40. To our knowledge, this is the first time the drug tetrabenazine has been tested in the 5XFAD mouse model of AD in a sex-stratified manner. Our results highlight 2 drugs (clomiphene citrate and Pik-90) from our previous computational work for further investigation. |
| first_indexed | 2024-03-11T03:34:53Z |
| format | Article |
| id | doaj.art-dcbacf36dc954ed09385abfc3a44fe05 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-11T03:34:53Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-dcbacf36dc954ed09385abfc3a44fe052023-11-18T02:08:36ZengMDPI AGLife2075-17292023-04-01135109510.3390/life13051095Preliminary In Vitro and In Vivo Insights of In Silico Candidate Repurposed Drugs for Alzheimer’s DiseaseKyriaki Savva0Margarita Zachariou1Demos Kynigopoulos2Eleni Fella3Maria-Ioanna Vitali4Xeni Kosofidou5Michail Spyrou6Irene Sargiannidou7Elena Panayiotou8Nikolas Dietis9George M. Spyrou10Bioinformatics Department, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, CyprusBioinformatics Department, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, CyprusDepartment of Neuropathology, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, CyprusDepartment of Neuropathology, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, CyprusExperimental Pharmacology Laboratory, Medical School, University of Cyprus, 2109 Nicosia, CyprusExperimental Pharmacology Laboratory, Medical School, University of Cyprus, 2109 Nicosia, CyprusExperimental Pharmacology Laboratory, Medical School, University of Cyprus, 2109 Nicosia, CyprusNeuroscience Department, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, CyprusDepartment of Neuropathology, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, CyprusExperimental Pharmacology Laboratory, Medical School, University of Cyprus, 2109 Nicosia, CyprusBioinformatics Department, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, CyprusAlzheimer’s disease (AD) is a progressive neurodegenerative disease and is the most common type of dementia. Although a considerably large amount of money has been invested in drug development for AD, no disease modifying treatment has been detected so far. In our previous work, we developed a computational method to highlight stage-specific candidate repurposed drugs against AD. In this study, we tested the effect of the top 13 candidate repurposed drugs that we proposed in our previous work in a severity stage-specific manner using an in vitro BACE1 assay and the effect of a top-ranked drug from the list of our previous work, tetrabenazine (TBZ), in the 5XFAD as an AD mouse model. From our in vitro screening, we detected 2 compounds (clomiphene citrate and Pik-90) that showed statistically significant inhibition against the activity of the BACE1 enzyme. The administration of TBZ at the selected dose and therapeutic regimen in 5XFAD in male and female mice showed no significant effect in behavioral tests using the Y-maze and the ELISA immunoassay of Aβ40. To our knowledge, this is the first time the drug tetrabenazine has been tested in the 5XFAD mouse model of AD in a sex-stratified manner. Our results highlight 2 drugs (clomiphene citrate and Pik-90) from our previous computational work for further investigation.https://www.mdpi.com/2075-1729/13/5/1095Alzheimer’s diseasein vitro testingin vivo testingin silico drug repurposing |
| spellingShingle | Kyriaki Savva Margarita Zachariou Demos Kynigopoulos Eleni Fella Maria-Ioanna Vitali Xeni Kosofidou Michail Spyrou Irene Sargiannidou Elena Panayiotou Nikolas Dietis George M. Spyrou Preliminary In Vitro and In Vivo Insights of In Silico Candidate Repurposed Drugs for Alzheimer’s Disease Life Alzheimer’s disease in vitro testing in vivo testing in silico drug repurposing |
| title | Preliminary In Vitro and In Vivo Insights of In Silico Candidate Repurposed Drugs for Alzheimer’s Disease |
| title_full | Preliminary In Vitro and In Vivo Insights of In Silico Candidate Repurposed Drugs for Alzheimer’s Disease |
| title_fullStr | Preliminary In Vitro and In Vivo Insights of In Silico Candidate Repurposed Drugs for Alzheimer’s Disease |
| title_full_unstemmed | Preliminary In Vitro and In Vivo Insights of In Silico Candidate Repurposed Drugs for Alzheimer’s Disease |
| title_short | Preliminary In Vitro and In Vivo Insights of In Silico Candidate Repurposed Drugs for Alzheimer’s Disease |
| title_sort | preliminary in vitro and in vivo insights of in silico candidate repurposed drugs for alzheimer s disease |
| topic | Alzheimer’s disease in vitro testing in vivo testing in silico drug repurposing |
| url | https://www.mdpi.com/2075-1729/13/5/1095 |
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