Wheat ergot fungus-derived and modified drug for inhibition of intracranial aneurysm rupture due to dysfunction of TLR-4 receptor in Alzheimer’s disease
<h4>Background</h4> Alzheimer’s disease (AD) is a form of dementia that strikes elderly people more frequently than it does younger people. The cognitive skills and memory of Alzheimer’s sufferers continue to deteriorate over time. Recent studies have shown that patients with AD have gre...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9851541/?tool=EBI |
| _version_ | 1797943936115802112 |
|---|---|
| author | Sandip Debnath Devesh Sharma Somdatta Yashwant Chaudhari Ritika Sharma Amir Afzal Shaikh Rahul Subhash Buchade Kavindra Kumar Kesari Abdel-Fattah M. Abdel-Fattah Mohammad Algahtani Mayyadah Mheidat Rawidh Alsaidalani Tapas Paul Amany A. Sayed Mohamed M. Abdel-Daim |
| author_facet | Sandip Debnath Devesh Sharma Somdatta Yashwant Chaudhari Ritika Sharma Amir Afzal Shaikh Rahul Subhash Buchade Kavindra Kumar Kesari Abdel-Fattah M. Abdel-Fattah Mohammad Algahtani Mayyadah Mheidat Rawidh Alsaidalani Tapas Paul Amany A. Sayed Mohamed M. Abdel-Daim |
| author_sort | Sandip Debnath |
| collection | DOAJ |
| description | <h4>Background</h4> Alzheimer’s disease (AD) is a form of dementia that strikes elderly people more frequently than it does younger people. The cognitive skills and memory of Alzheimer’s sufferers continue to deteriorate over time. Recent studies have shown that patients with AD have greater amounts of inflammatory markers in their bodies, which suggests that inflammation occurs early on in the progression of the disease. There is a possibility that Aß oligomers and fibrils can be recognised by TLRs, in addition to the microglial receptors CD14, CD36, and CD47. When Aß binds to either CD36 or TLR4, it sets off a chain reaction of inflammatory chemokines and cytokines that ultimately results in neurodegeneration. Diabetes and Alzheimer’s disease have both been recently related to TLR4. The activation of TLR4 has been connected to a variety of clinical difficulties that are associated with diabetes, in addition to the internal environment of the body and the microenvironment of the brain. TLR4 inhibitors have been shown in clinical investigations to not only lessen the likelihood of getting sick but also to increase the average longevity. <h4>Result</h4> In this work we used molecular docking and molecular dynamics modelling to investigate the effectiveness of FDA-approved antidiabetic plant derived drugs in combating the TLR4 receptor. Molecular docking experiments were used to make a prediction regarding the most important interactions involving 2-Bromoergocryptine Mesylate. With a binding affinity of -8.26 kcal/mol, it stood out from the other candidates as the one with the greatest potential. To verify the interaction pattern that takes place between 2-Bromoergocryptine Mesylate and the TLR4 receptor, a molecular dynamic simulation was run at a time scale of 150 nanoseconds. Because of this, 2-Bromoergocryptine Mesylate was able to make substantial contact with the active site, which led to increased structural stability during the process of the complex’s dynamic development. <h4>Conclusion</h4> As a result of this, the results of our research may be relevant for future research into the efficacy of 2-bromoergocryptine mesylate as a potential lead treatment for TLR4 receptors in intracranial aneurysm rupture in AD. |
| first_indexed | 2024-04-10T20:32:00Z |
| format | Article |
| id | doaj.art-a86eee00a062447b91fbe44f76843836 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-10T20:32:00Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a86eee00a062447b91fbe44f768438362023-01-25T05:33:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01181Wheat ergot fungus-derived and modified drug for inhibition of intracranial aneurysm rupture due to dysfunction of TLR-4 receptor in Alzheimer’s diseaseSandip DebnathDevesh SharmaSomdatta Yashwant ChaudhariRitika SharmaAmir Afzal ShaikhRahul Subhash BuchadeKavindra Kumar KesariAbdel-Fattah M. Abdel-FattahMohammad AlgahtaniMayyadah MheidatRawidh AlsaidalaniTapas PaulAmany A. SayedMohamed M. Abdel-Daim<h4>Background</h4> Alzheimer’s disease (AD) is a form of dementia that strikes elderly people more frequently than it does younger people. The cognitive skills and memory of Alzheimer’s sufferers continue to deteriorate over time. Recent studies have shown that patients with AD have greater amounts of inflammatory markers in their bodies, which suggests that inflammation occurs early on in the progression of the disease. There is a possibility that Aß oligomers and fibrils can be recognised by TLRs, in addition to the microglial receptors CD14, CD36, and CD47. When Aß binds to either CD36 or TLR4, it sets off a chain reaction of inflammatory chemokines and cytokines that ultimately results in neurodegeneration. Diabetes and Alzheimer’s disease have both been recently related to TLR4. The activation of TLR4 has been connected to a variety of clinical difficulties that are associated with diabetes, in addition to the internal environment of the body and the microenvironment of the brain. TLR4 inhibitors have been shown in clinical investigations to not only lessen the likelihood of getting sick but also to increase the average longevity. <h4>Result</h4> In this work we used molecular docking and molecular dynamics modelling to investigate the effectiveness of FDA-approved antidiabetic plant derived drugs in combating the TLR4 receptor. Molecular docking experiments were used to make a prediction regarding the most important interactions involving 2-Bromoergocryptine Mesylate. With a binding affinity of -8.26 kcal/mol, it stood out from the other candidates as the one with the greatest potential. To verify the interaction pattern that takes place between 2-Bromoergocryptine Mesylate and the TLR4 receptor, a molecular dynamic simulation was run at a time scale of 150 nanoseconds. Because of this, 2-Bromoergocryptine Mesylate was able to make substantial contact with the active site, which led to increased structural stability during the process of the complex’s dynamic development. <h4>Conclusion</h4> As a result of this, the results of our research may be relevant for future research into the efficacy of 2-bromoergocryptine mesylate as a potential lead treatment for TLR4 receptors in intracranial aneurysm rupture in AD.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9851541/?tool=EBI |
| spellingShingle | Sandip Debnath Devesh Sharma Somdatta Yashwant Chaudhari Ritika Sharma Amir Afzal Shaikh Rahul Subhash Buchade Kavindra Kumar Kesari Abdel-Fattah M. Abdel-Fattah Mohammad Algahtani Mayyadah Mheidat Rawidh Alsaidalani Tapas Paul Amany A. Sayed Mohamed M. Abdel-Daim Wheat ergot fungus-derived and modified drug for inhibition of intracranial aneurysm rupture due to dysfunction of TLR-4 receptor in Alzheimer’s disease PLoS ONE |
| title | Wheat ergot fungus-derived and modified drug for inhibition of intracranial aneurysm rupture due to dysfunction of TLR-4 receptor in Alzheimer’s disease |
| title_full | Wheat ergot fungus-derived and modified drug for inhibition of intracranial aneurysm rupture due to dysfunction of TLR-4 receptor in Alzheimer’s disease |
| title_fullStr | Wheat ergot fungus-derived and modified drug for inhibition of intracranial aneurysm rupture due to dysfunction of TLR-4 receptor in Alzheimer’s disease |
| title_full_unstemmed | Wheat ergot fungus-derived and modified drug for inhibition of intracranial aneurysm rupture due to dysfunction of TLR-4 receptor in Alzheimer’s disease |
| title_short | Wheat ergot fungus-derived and modified drug for inhibition of intracranial aneurysm rupture due to dysfunction of TLR-4 receptor in Alzheimer’s disease |
| title_sort | wheat ergot fungus derived and modified drug for inhibition of intracranial aneurysm rupture due to dysfunction of tlr 4 receptor in alzheimer s disease |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9851541/?tool=EBI |
| work_keys_str_mv | AT sandipdebnath wheatergotfungusderivedandmodifieddrugforinhibitionofintracranialaneurysmruptureduetodysfunctionoftlr4receptorinalzheimersdisease AT deveshsharma wheatergotfungusderivedandmodifieddrugforinhibitionofintracranialaneurysmruptureduetodysfunctionoftlr4receptorinalzheimersdisease AT somdattayashwantchaudhari wheatergotfungusderivedandmodifieddrugforinhibitionofintracranialaneurysmruptureduetodysfunctionoftlr4receptorinalzheimersdisease AT ritikasharma wheatergotfungusderivedandmodifieddrugforinhibitionofintracranialaneurysmruptureduetodysfunctionoftlr4receptorinalzheimersdisease AT amirafzalshaikh wheatergotfungusderivedandmodifieddrugforinhibitionofintracranialaneurysmruptureduetodysfunctionoftlr4receptorinalzheimersdisease AT rahulsubhashbuchade wheatergotfungusderivedandmodifieddrugforinhibitionofintracranialaneurysmruptureduetodysfunctionoftlr4receptorinalzheimersdisease AT kavindrakumarkesari wheatergotfungusderivedandmodifieddrugforinhibitionofintracranialaneurysmruptureduetodysfunctionoftlr4receptorinalzheimersdisease AT abdelfattahmabdelfattah wheatergotfungusderivedandmodifieddrugforinhibitionofintracranialaneurysmruptureduetodysfunctionoftlr4receptorinalzheimersdisease AT mohammadalgahtani wheatergotfungusderivedandmodifieddrugforinhibitionofintracranialaneurysmruptureduetodysfunctionoftlr4receptorinalzheimersdisease AT mayyadahmheidat wheatergotfungusderivedandmodifieddrugforinhibitionofintracranialaneurysmruptureduetodysfunctionoftlr4receptorinalzheimersdisease AT rawidhalsaidalani wheatergotfungusderivedandmodifieddrugforinhibitionofintracranialaneurysmruptureduetodysfunctionoftlr4receptorinalzheimersdisease AT tapaspaul wheatergotfungusderivedandmodifieddrugforinhibitionofintracranialaneurysmruptureduetodysfunctionoftlr4receptorinalzheimersdisease AT amanyasayed wheatergotfungusderivedandmodifieddrugforinhibitionofintracranialaneurysmruptureduetodysfunctionoftlr4receptorinalzheimersdisease AT mohamedmabdeldaim wheatergotfungusderivedandmodifieddrugforinhibitionofintracranialaneurysmruptureduetodysfunctionoftlr4receptorinalzheimersdisease |