{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:21:45Z","timestamp":1790623305991,"version":"4.1.0"},"reference-count":67,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T00:00:00Z","timestamp":1644364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1A2C2095412"],"award-info":[{"award-number":["2021R1A2C2095412"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hundreds of millions of people around the world have been affected by Type 2 diabetes (T2D) which is a metabolic disorder. Clinical research has revealed T2D as a possible risk factor for Alzheimer\u2019s disease (AD) development (and vice versa). Amyloid-\u03b2 (A\u03b2) and human islet amyloid polypeptide are the main pathological species in AD and T2D, respectively. However, the mechanisms by which these two amyloidogenic peptides co-aggregate are largely uninvestigated. Herein, for the first time, we present the cross-seeding between Amylin1-37 and A\u03b240 considering the particular effect of the histidine tautomerism at atomic resolution applying the all-atom molecular dynamics (MD) simulations for heterodimeric complexes. The results via random seed MD simulations indicated that the A\u03b240(\u03b4\u03b4\u03b4) isomer in cross-talking with Islet(\u03b5) and Islet(\u03b4) isomers could retain or increase the \u03b2-sheet content in its structure that may make it more prone to further aggregation and exhibit higher toxicity. The other tautomeric isomers which initially did not have a \u03b2-sheet structure in their monomeric forms did not show any generated \u03b2-sheet, except for one seed of the Islet(\u03b5) and A\u03b240(\u03b5\u03b5\u03b5) heterodimers complex that displayed a small amount of formed \u03b2-sheet. This computational research may provide a different point of view to examine all possible parameters that may contribute to the development of AD and T2D and provide a better understanding of the pathological link between these two severe diseases.<\/jats:p>","DOI":"10.3390\/ijms23041930","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T21:22:15Z","timestamp":1644441735000},"page":"1930","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mechanistic Insights into the Polymorphic Associations and Cross-Seeding of A\u03b2 and hIAPP in the Presence of Histidine Tautomerism: An All-Atom Molecular Dynamic Study"],"prefix":"10.3390","volume":"23","author":[{"given":"Abbas","family":"Salimi","sequence":"first","affiliation":[{"name":"Department of Chemistry, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sompriya","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Yong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1021\/acschemneuro.6b00247","article-title":"Molecular Understanding of A\u03b2-hIAPP Cross-Seeding Assemblies on Lipid Membranes","volume":"8","author":"Zhang","year":"2017","journal-title":"ACS Chem. 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