Structural Analysis of Amylin and Amyloid β Peptide Signaling in Alzheimer’s Disease
Amylin and amyloid β belong to the same protein family and activate the same receptors. Amyloid β levels are elevated in Alzheimer’s disease. Recent studies have demonstrated that amylin-based peptides can reduce the symptoms of Alzheimer’s disease in animal models. Replica exchange molecular dynami...
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MDPI AG
2025-01-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/15/1/89 |
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| author | Longsheng Xie Christopher Lockhart Steven R. Bowers Dmitri K. Klimov Mohsin Saleet Jafri |
| author_facet | Longsheng Xie Christopher Lockhart Steven R. Bowers Dmitri K. Klimov Mohsin Saleet Jafri |
| author_sort | Longsheng Xie |
| collection | DOAJ |
| description | Amylin and amyloid β belong to the same protein family and activate the same receptors. Amyloid β levels are elevated in Alzheimer’s disease. Recent studies have demonstrated that amylin-based peptides can reduce the symptoms of Alzheimer’s disease in animal models. Replica exchange molecular dynamics simulation machine learning, as well as other computational analyses, were applied to improve the understanding of the amino acid residues in these amylin-based peptides. Comparisons were made between amylin, amylin-based peptides, and amyloid β. These studies converged on amylin residues 10Q, 28S, 29S, 30T, 31N, 32V, 33G, 34S, and 35N (residues 10 and 28–35) being ranked highest, meaning that they were the most likely to be involved in activating the same targets as amyloid β. Surprisingly, the amyloid β signaling domain most closely matched amylin residues 29–35 in the simulated structures. These findings suggest important residues that are structurally similar between amylin and amyloid β and are thus implicated in the activation of the amylin receptor. |
| format | Article |
| id | doaj-art-eb60a3c3d1d04d76a1111510d9339c2e |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-eb60a3c3d1d04d76a1111510d9339c2e2025-01-24T13:25:08ZengMDPI AGBiomolecules2218-273X2025-01-011518910.3390/biom15010089Structural Analysis of Amylin and Amyloid β Peptide Signaling in Alzheimer’s DiseaseLongsheng Xie0Christopher Lockhart1Steven R. Bowers2Dmitri K. Klimov3Mohsin Saleet Jafri4School of Systems Biology, George Mason University, Fairfax, VA 22030, USASchool of Systems Biology, George Mason University, Fairfax, VA 22030, USASchool of Systems Biology, George Mason University, Fairfax, VA 22030, USASchool of Systems Biology, George Mason University, Fairfax, VA 22030, USASchool of Systems Biology, George Mason University, Fairfax, VA 22030, USAAmylin and amyloid β belong to the same protein family and activate the same receptors. Amyloid β levels are elevated in Alzheimer’s disease. Recent studies have demonstrated that amylin-based peptides can reduce the symptoms of Alzheimer’s disease in animal models. Replica exchange molecular dynamics simulation machine learning, as well as other computational analyses, were applied to improve the understanding of the amino acid residues in these amylin-based peptides. Comparisons were made between amylin, amylin-based peptides, and amyloid β. These studies converged on amylin residues 10Q, 28S, 29S, 30T, 31N, 32V, 33G, 34S, and 35N (residues 10 and 28–35) being ranked highest, meaning that they were the most likely to be involved in activating the same targets as amyloid β. Surprisingly, the amyloid β signaling domain most closely matched amylin residues 29–35 in the simulated structures. These findings suggest important residues that are structurally similar between amylin and amyloid β and are thus implicated in the activation of the amylin receptor.https://www.mdpi.com/2218-273X/15/1/89Alzheimer’s diseaseamylinamyloid βmolecular dynamics simulationmachine learning |
| spellingShingle | Longsheng Xie Christopher Lockhart Steven R. Bowers Dmitri K. Klimov Mohsin Saleet Jafri Structural Analysis of Amylin and Amyloid β Peptide Signaling in Alzheimer’s Disease Biomolecules Alzheimer’s disease amylin amyloid β molecular dynamics simulation machine learning |
| title | Structural Analysis of Amylin and Amyloid β Peptide Signaling in Alzheimer’s Disease |
| title_full | Structural Analysis of Amylin and Amyloid β Peptide Signaling in Alzheimer’s Disease |
| title_fullStr | Structural Analysis of Amylin and Amyloid β Peptide Signaling in Alzheimer’s Disease |
| title_full_unstemmed | Structural Analysis of Amylin and Amyloid β Peptide Signaling in Alzheimer’s Disease |
| title_short | Structural Analysis of Amylin and Amyloid β Peptide Signaling in Alzheimer’s Disease |
| title_sort | structural analysis of amylin and amyloid β peptide signaling in alzheimer s disease |
| topic | Alzheimer’s disease amylin amyloid β molecular dynamics simulation machine learning |
| url | https://www.mdpi.com/2218-273X/15/1/89 |
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