Unraveling human transferrin-tryptamine interactions: a computational and biophysical approach to Alzheimer’s disease therapeutics
Neurodegeneration is a progressive loss of neurons that leads to affected cognitive and motor functions and is characterized by neurodegenerative disorders (NDs). Human transferrin (Htf) is a blood plasma glycoprotein that binds to iron and regulates the free iron in biological fluids. Free iron is...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1540736/full |
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| author | Mohammed Alrouji Mohammed S. Alshammari Taghreed A. Majrashi Azna Zuberi Moyad Shahwan Akhtar Atiya Anas Shamsi |
| author_facet | Mohammed Alrouji Mohammed S. Alshammari Taghreed A. Majrashi Azna Zuberi Moyad Shahwan Akhtar Atiya Anas Shamsi |
| author_sort | Mohammed Alrouji |
| collection | DOAJ |
| description | Neurodegeneration is a progressive loss of neurons that leads to affected cognitive and motor functions and is characterized by neurodegenerative disorders (NDs). Human transferrin (Htf) is a blood plasma glycoprotein that binds to iron and regulates the free iron in biological fluids. Free iron is a potent neurotoxin associated with the generation of Reactive oxygen species (ROS) and is ultimately linked to oxidative stress and neuronal damage. Thus, targeting iron homeostasis is an attractive strategy for the management of NDs, viz. Alzheimer's disease (AD). Tryptamine (Trp) is a naturally occurring monoamine, that has demonstrated promising roles in AD therapeutics. The present study aims to delineate the binding mechanism of Trp with Htf employing computational and spectroscopic approaches. Molecular docking ascertained the vital residues governing the Htf-Trp complex formation. Further, Molecular dynamic (MD) studies ascertained the structural dynamics and stability of the complex, implying that the binding of Trp causes minimal structural alterations in Htf, suggestive of the stability of the complex. The results from fluorescence spectroscopy demonstrated the binding of Trp with Htf with a binding constant (K) of 0.48 × 106 M−1, validating the in silico observations. This study provides a platform to understand the binding mechanism that may lead to novel therapeutic approaches targeting AD. |
| format | Article |
| id | doaj-art-1db16c7ee8344ebd98ef31254c0747e7 |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-1db16c7ee8344ebd98ef31254c0747e72025-08-20T02:51:53ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-03-011610.3389/fphar.2025.15407361540736Unraveling human transferrin-tryptamine interactions: a computational and biophysical approach to Alzheimer’s disease therapeuticsMohammed Alrouji0Mohammed S. Alshammari1Taghreed A. Majrashi2Azna Zuberi3Moyad Shahwan4Akhtar Atiya5Anas Shamsi6Department of Medical Laboratories, College of Applied Medical Sciences, Shaqra University, Shaqra, Saudi ArabiaDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Shaqra, Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, King Khalid University, Abha, Saudi ArabiaDivision of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesCenter for Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab EmiratesDepartment of Basic Medical Sciences, College of Applied Medical Sciences, King Khalid University (KKU), Muhayil, Asir, Saudi ArabiaCenter for Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab EmiratesNeurodegeneration is a progressive loss of neurons that leads to affected cognitive and motor functions and is characterized by neurodegenerative disorders (NDs). Human transferrin (Htf) is a blood plasma glycoprotein that binds to iron and regulates the free iron in biological fluids. Free iron is a potent neurotoxin associated with the generation of Reactive oxygen species (ROS) and is ultimately linked to oxidative stress and neuronal damage. Thus, targeting iron homeostasis is an attractive strategy for the management of NDs, viz. Alzheimer's disease (AD). Tryptamine (Trp) is a naturally occurring monoamine, that has demonstrated promising roles in AD therapeutics. The present study aims to delineate the binding mechanism of Trp with Htf employing computational and spectroscopic approaches. Molecular docking ascertained the vital residues governing the Htf-Trp complex formation. Further, Molecular dynamic (MD) studies ascertained the structural dynamics and stability of the complex, implying that the binding of Trp causes minimal structural alterations in Htf, suggestive of the stability of the complex. The results from fluorescence spectroscopy demonstrated the binding of Trp with Htf with a binding constant (K) of 0.48 × 106 M−1, validating the in silico observations. This study provides a platform to understand the binding mechanism that may lead to novel therapeutic approaches targeting AD.https://www.frontiersin.org/articles/10.3389/fphar.2025.1540736/fullAlzheimer’s diseasehuman transferrinmolecular dockingmolecular dynamics simulationfluorescence spectroscopy |
| spellingShingle | Mohammed Alrouji Mohammed S. Alshammari Taghreed A. Majrashi Azna Zuberi Moyad Shahwan Akhtar Atiya Anas Shamsi Unraveling human transferrin-tryptamine interactions: a computational and biophysical approach to Alzheimer’s disease therapeutics Frontiers in Pharmacology Alzheimer’s disease human transferrin molecular docking molecular dynamics simulation fluorescence spectroscopy |
| title | Unraveling human transferrin-tryptamine interactions: a computational and biophysical approach to Alzheimer’s disease therapeutics |
| title_full | Unraveling human transferrin-tryptamine interactions: a computational and biophysical approach to Alzheimer’s disease therapeutics |
| title_fullStr | Unraveling human transferrin-tryptamine interactions: a computational and biophysical approach to Alzheimer’s disease therapeutics |
| title_full_unstemmed | Unraveling human transferrin-tryptamine interactions: a computational and biophysical approach to Alzheimer’s disease therapeutics |
| title_short | Unraveling human transferrin-tryptamine interactions: a computational and biophysical approach to Alzheimer’s disease therapeutics |
| title_sort | unraveling human transferrin tryptamine interactions a computational and biophysical approach to alzheimer s disease therapeutics |
| topic | Alzheimer’s disease human transferrin molecular docking molecular dynamics simulation fluorescence spectroscopy |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1540736/full |
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