Unraveling the Binding Mechanism of Alzheimer’s Drugs with Irisin: Spectroscopic, Calorimetric, and Computational Approaches
The prevalence of Alzheimer’s disease (AD) has been a major health concern for a long time. Despite recent progress, there is still a strong need to develop effective disease-modifying therapies. Several drugs have already been approved to retard the progression of AD-related symptoms; however, ther...
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MDPI AG
2022-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/11/5965 |
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| author | Rashid Waseem Anas Shamsi Tanzeel Khan Md. Imtaiyaz Hassan Syed Naqui Kazim Mohammad Shahid Asimul Islam |
| author_facet | Rashid Waseem Anas Shamsi Tanzeel Khan Md. Imtaiyaz Hassan Syed Naqui Kazim Mohammad Shahid Asimul Islam |
| author_sort | Rashid Waseem |
| collection | DOAJ |
| description | The prevalence of Alzheimer’s disease (AD) has been a major health concern for a long time. Despite recent progress, there is still a strong need to develop effective disease-modifying therapies. Several drugs have already been approved to retard the progression of AD-related symptoms; however, there is a need to develop an effective carrier system for the delivery of drugs to combat such diseases. In recent years, various biological macromolecules, including proteins, have been used as carriers for drug delivery. Irisin is a beneficial hormone in such diseases, including AD and related pathologies. Herein, the interaction mechanism of irisin with AD drugs such as memantine, galantamine, and fluoxetine is investigated. Fluorescence studies revealed that the above drugs bind to irisin with significant affinity, with fluoxetine having the highest binding affinity. Isothermal titration calorimetry (ITC) complemented the spontaneous binding of these drugs with irisin, delineating various associated thermodynamic and binding parameters. Molecular docking further validated the fluorescence and ITC results and unfolded the mechanism that hydrogen bonding governs the binding of fluoxetine to irisin with a significant binding score, i.e., −6.3 kcal/mol. We believe that these findings provide a promising solution to fight against AD as well as a platform for further research to utilize irisin in the drug-delivery system for an effective therapeutic strategy. |
| first_indexed | 2024-03-10T01:17:28Z |
| format | Article |
| id | doaj.art-ca29edd492a5440a829f4571e384fab9 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:17:28Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ca29edd492a5440a829f4571e384fab92023-11-23T14:07:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-012311596510.3390/ijms23115965Unraveling the Binding Mechanism of Alzheimer’s Drugs with Irisin: Spectroscopic, Calorimetric, and Computational ApproachesRashid Waseem0Anas Shamsi1Tanzeel Khan2Md. Imtaiyaz Hassan3Syed Naqui Kazim4Mohammad Shahid5Asimul Islam6Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, IndiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, IndiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, IndiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, IndiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, IndiaDepartment of Basic Medical Sciences, College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi ArabiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, IndiaThe prevalence of Alzheimer’s disease (AD) has been a major health concern for a long time. Despite recent progress, there is still a strong need to develop effective disease-modifying therapies. Several drugs have already been approved to retard the progression of AD-related symptoms; however, there is a need to develop an effective carrier system for the delivery of drugs to combat such diseases. In recent years, various biological macromolecules, including proteins, have been used as carriers for drug delivery. Irisin is a beneficial hormone in such diseases, including AD and related pathologies. Herein, the interaction mechanism of irisin with AD drugs such as memantine, galantamine, and fluoxetine is investigated. Fluorescence studies revealed that the above drugs bind to irisin with significant affinity, with fluoxetine having the highest binding affinity. Isothermal titration calorimetry (ITC) complemented the spontaneous binding of these drugs with irisin, delineating various associated thermodynamic and binding parameters. Molecular docking further validated the fluorescence and ITC results and unfolded the mechanism that hydrogen bonding governs the binding of fluoxetine to irisin with a significant binding score, i.e., −6.3 kcal/mol. We believe that these findings provide a promising solution to fight against AD as well as a platform for further research to utilize irisin in the drug-delivery system for an effective therapeutic strategy.https://www.mdpi.com/1422-0067/23/11/5965irisinmolecular dockingfluorescence spectroscopydrug deliveryAlzheimer’s diseaseisothermal titration calorimetry |
| spellingShingle | Rashid Waseem Anas Shamsi Tanzeel Khan Md. Imtaiyaz Hassan Syed Naqui Kazim Mohammad Shahid Asimul Islam Unraveling the Binding Mechanism of Alzheimer’s Drugs with Irisin: Spectroscopic, Calorimetric, and Computational Approaches International Journal of Molecular Sciences irisin molecular docking fluorescence spectroscopy drug delivery Alzheimer’s disease isothermal titration calorimetry |
| title | Unraveling the Binding Mechanism of Alzheimer’s Drugs with Irisin: Spectroscopic, Calorimetric, and Computational Approaches |
| title_full | Unraveling the Binding Mechanism of Alzheimer’s Drugs with Irisin: Spectroscopic, Calorimetric, and Computational Approaches |
| title_fullStr | Unraveling the Binding Mechanism of Alzheimer’s Drugs with Irisin: Spectroscopic, Calorimetric, and Computational Approaches |
| title_full_unstemmed | Unraveling the Binding Mechanism of Alzheimer’s Drugs with Irisin: Spectroscopic, Calorimetric, and Computational Approaches |
| title_short | Unraveling the Binding Mechanism of Alzheimer’s Drugs with Irisin: Spectroscopic, Calorimetric, and Computational Approaches |
| title_sort | unraveling the binding mechanism of alzheimer s drugs with irisin spectroscopic calorimetric and computational approaches |
| topic | irisin molecular docking fluorescence spectroscopy drug delivery Alzheimer’s disease isothermal titration calorimetry |
| url | https://www.mdpi.com/1422-0067/23/11/5965 |
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