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Study has revealed that T2D is a major risk factor of AD, and thus exploring therapeutic approaches that can target both diseases has drawn much interest in recent years. In this study, we tried to explore drugs that could be potentially used to prevent or treat both AD and T2D via a drug repositioning approach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We first searched the known drugs that may be effective to T2D treatment based on the network distance between the T2D\u2010associated genes and drugs deposited in the DrugBank database. Then, via molecular docking, we further screened these drugs by examining their interaction with islet amyloid polypeptide (IAPP) and A\u03b242 peptide, the key components involved in the pathogenesis of T2D or AD. Finally, the binding between the selected drug candidates and the target proteins was verified by molecular dynamics (MD) simulation; and the potential function of the drug candidates and the corresponding targets were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>From multiple resources, 734 T2D\u2010associated genes were collected, and a list of 1109 drug candidates for T2D was obtained. We found that hypericin had the lowest binding energy and the most stable interaction with either IAPP or A\u03b242 peptide. In addition, we also found that the target genes regulated by hypericin were differentially expressed in the tissues related to the two diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results show that hypericin may be able to bind with IAPP and A\u03b242 stably and prevent their accumulation, and thus could be a promising drug candidate for treating the comorbidity of AD and T2D.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14260","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T06:30:04Z","timestamp":1684132204000},"page":"3307-3321","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Hypericin as a potential drug for treating Alzheimer's disease and type 2 diabetes with a view to drug 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