Decoding Conformational Imprint of Convoluted Molecular Interactions Between Prenylflavonoids and Aggregated Amyloid-Beta42 Peptide Causing Alzheimer’s Disease
Protein misfolding occurs due to the loss of native protein structure and adopts an abnormal structure, wherein the misfolded proteins accumulate and form aggregates, which result in the formation of amyloid fibrils that are associated with neurodegenerative diseases. Amyloid beta (Aβ42) aggregation...
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2021.753146/full |
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| author | E. Srinivasan E. Srinivasan G. Chandrasekhar P. Chandrasekar K. Anbarasu AS Vickram Iftikhar Aslam Tayubi R. Rajasekaran Rohini Karunakaran |
| author_facet | E. Srinivasan E. Srinivasan G. Chandrasekhar P. Chandrasekar K. Anbarasu AS Vickram Iftikhar Aslam Tayubi R. Rajasekaran Rohini Karunakaran |
| author_sort | E. Srinivasan |
| collection | DOAJ |
| description | Protein misfolding occurs due to the loss of native protein structure and adopts an abnormal structure, wherein the misfolded proteins accumulate and form aggregates, which result in the formation of amyloid fibrils that are associated with neurodegenerative diseases. Amyloid beta (Aβ42) aggregation or amyloidosis is contemplated as a unique hallmark characteristic of Alzheimer’s disease (AD). Due to aberrant accrual and aggregation of Aβ42 in extracellular space, the formation of senile plaques is found in AD patients. These senile plaques occur usually in the cognitive and memory region of the brain, enfeebles neurodegeneration, hinders the signaling between synapse, and disrupts neuronal functioning. In recent years, herbal compounds are identified and characterized for their potential as Aβ42 inhibitors. Thus, understanding their structure and molecular mechanics can provide an incredible finding in AD therapeutics. To describe the structure-based molecular studies in the rational designing of drugs against amyloid fibrils, we examined various herbal compounds that belong to prenylflavonoids. The present study characterizes the trends we identified at molecular docking studies and dynamics simulation where we observed stronger binding orientation of bavachalcone, bavachin, and neobavaisoflavone with the amyloid-beta (Aβ42) fibril structure. Hence, we could postulate that these herbal compounds could be potential inhibitors of Aβ42 fibrils; these anti-aggregation agents need to be considered in treating AD. |
| first_indexed | 2024-12-22T00:04:05Z |
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| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-22T00:04:05Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-f18a7b168f73466ea556547368b5f9d32022-12-21T18:45:37ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462021-12-01910.3389/fchem.2021.753146753146Decoding Conformational Imprint of Convoluted Molecular Interactions Between Prenylflavonoids and Aggregated Amyloid-Beta42 Peptide Causing Alzheimer’s DiseaseE. Srinivasan0E. Srinivasan1G. Chandrasekhar2P. Chandrasekar3K. Anbarasu4AS Vickram5Iftikhar Aslam Tayubi6R. Rajasekaran7Rohini Karunakaran8Bioinformatics Lab, Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology (Deemed to be University), Vellore, IndiaDepartment of Bioinformatics, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, IndiaBioinformatics Lab, Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology (Deemed to be University), Vellore, IndiaBioinformatics Lab, Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology (Deemed to be University), Vellore, IndiaDepartment of Bioinformatics, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, IndiaDepartment of Biotechnology, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, IndiaFaculty of Computing and Information Technology, King Abdulaziz University, Jeddah, Saudi ArabiaBioinformatics Lab, Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology (Deemed to be University), Vellore, IndiaUnit of Biochemistry, Faculty of Medicine, AIMST University, Bedong, MalaysiaProtein misfolding occurs due to the loss of native protein structure and adopts an abnormal structure, wherein the misfolded proteins accumulate and form aggregates, which result in the formation of amyloid fibrils that are associated with neurodegenerative diseases. Amyloid beta (Aβ42) aggregation or amyloidosis is contemplated as a unique hallmark characteristic of Alzheimer’s disease (AD). Due to aberrant accrual and aggregation of Aβ42 in extracellular space, the formation of senile plaques is found in AD patients. These senile plaques occur usually in the cognitive and memory region of the brain, enfeebles neurodegeneration, hinders the signaling between synapse, and disrupts neuronal functioning. In recent years, herbal compounds are identified and characterized for their potential as Aβ42 inhibitors. Thus, understanding their structure and molecular mechanics can provide an incredible finding in AD therapeutics. To describe the structure-based molecular studies in the rational designing of drugs against amyloid fibrils, we examined various herbal compounds that belong to prenylflavonoids. The present study characterizes the trends we identified at molecular docking studies and dynamics simulation where we observed stronger binding orientation of bavachalcone, bavachin, and neobavaisoflavone with the amyloid-beta (Aβ42) fibril structure. Hence, we could postulate that these herbal compounds could be potential inhibitors of Aβ42 fibrils; these anti-aggregation agents need to be considered in treating AD.https://www.frontiersin.org/articles/10.3389/fchem.2021.753146/fullalzheimer’samyloid-betaneobavaisoflavoneherbal active compoundscomputational screening |
| spellingShingle | E. Srinivasan E. Srinivasan G. Chandrasekhar P. Chandrasekar K. Anbarasu AS Vickram Iftikhar Aslam Tayubi R. Rajasekaran Rohini Karunakaran Decoding Conformational Imprint of Convoluted Molecular Interactions Between Prenylflavonoids and Aggregated Amyloid-Beta42 Peptide Causing Alzheimer’s Disease Frontiers in Chemistry alzheimer’s amyloid-beta neobavaisoflavone herbal active compounds computational screening |
| title | Decoding Conformational Imprint of Convoluted Molecular Interactions Between Prenylflavonoids and Aggregated Amyloid-Beta42 Peptide Causing Alzheimer’s Disease |
| title_full | Decoding Conformational Imprint of Convoluted Molecular Interactions Between Prenylflavonoids and Aggregated Amyloid-Beta42 Peptide Causing Alzheimer’s Disease |
| title_fullStr | Decoding Conformational Imprint of Convoluted Molecular Interactions Between Prenylflavonoids and Aggregated Amyloid-Beta42 Peptide Causing Alzheimer’s Disease |
| title_full_unstemmed | Decoding Conformational Imprint of Convoluted Molecular Interactions Between Prenylflavonoids and Aggregated Amyloid-Beta42 Peptide Causing Alzheimer’s Disease |
| title_short | Decoding Conformational Imprint of Convoluted Molecular Interactions Between Prenylflavonoids and Aggregated Amyloid-Beta42 Peptide Causing Alzheimer’s Disease |
| title_sort | decoding conformational imprint of convoluted molecular interactions between prenylflavonoids and aggregated amyloid beta42 peptide causing alzheimer s disease |
| topic | alzheimer’s amyloid-beta neobavaisoflavone herbal active compounds computational screening |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2021.753146/full |
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