{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T17:46:22Z","timestamp":1792431982063,"version":"4.5.0"},"reference-count":46,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) has become common as the number of aged people increases making it as a socioeconomic problem lately. To date, no success is recorded for disease-modifying therapies for AD but only drugs for symptomatic relief exist. Research has been centered on the role of amyloid-\u03b2 on the pathogenesis of AD, which has led to the development of drugs that target A\u03b2 (\u03b2- and \u03b3-secretase inhibitors) to reduce the amount of A\u03b2 formed. However, the existing \u03b2 and \u03b3-secretase inhibitors were associated with harmful side effects, low efficacy, and inability to cross the blood-brain barrier.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      This study therefore used\n                      <jats:italic>in silico<\/jats:italic>\n                      approach to predict the inhibitory properties of alkaloids as potential drug targets against AD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Thus, in this current study, 54 alkaloids from the PhytoHub server (phytohub.eu), and two approved drugs were docked against \u03b2-secretases. Additionally, galantamine and 5 alkaloids with the utmost binding potential with \u03b2-secretase were subjected to pharmacokinetics evaluation and docked against \u03b3-secretase.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>From the result, 5 compounds displayed for both docking periods, with demissidine, solasodine, tomatidine, and solanidine having better BE than the control drugs. Based on the pharmacokinetics evaluation, 4 compounds possessed good pharmacokinetic evaluation and biological activities than galantamine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study suggests that demissidine, solasodine, tomatidine, and solanidine are promising dual inhibitors against \u03b2- and \u03b3-secretase proteins\n                      <jats:italic>in silico<\/jats:italic>\n                      . However, there is an urgent need to carry out in vitro and in vivo experiments on these new leads to validate the findings of this study.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877241313049","type":"journal-article","created":{"date-parts":[[2025,2,16]],"date-time":"2025-02-16T23:42:31Z","timestamp":1739749351000},"page":"1191-1215","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["<i>In silico<\/i>\n                    study of selected alkaloids as dual inhibitors of \u03b2- and \u03b3-secretases for Alzheimer's disease"],"prefix":"10.1177","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8062-5873","authenticated-orcid":false,"given":"Isreal Ayobami","family":"Onifade","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, University at Albany - State University of New York, Albany, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9427-9804","authenticated-orcid":false,"given":"Haruna Isiyaku","family":"Umar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Federal University of Technology, Akure, Nigeria"},{"name":"Computer-Aided Therapeutic Discovery and Design Platform, Federal University of Technology, Akure, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullahi Tunde","family":"Aborode","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Healthy Africans Platform, Ibadan, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aeshah A","family":"Awaji","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, University College of Taymaa, University of Tabuk, Tabuk, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2020-5734","authenticated-orcid":false,"given":"Ifeoluwapo Deborah","family":"Jegede","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Syracuse University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0607-8255","authenticated-orcid":false,"given":"Bunmi Helen","family":"Adeleye","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Huddersfield, Huddersfield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8500-2018","authenticated-orcid":false,"given":"Dorcas Oladayo","family":"Fatoba","sequence":"additional","affiliation":[{"name":"The University of Tennessee Health Science Center, Memphis, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6095-5883","authenticated-orcid":false,"given":"Ridwan Opeyemi","family":"Bello","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Queensland, Brisbane, \rAustralia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7717-105X","authenticated-orcid":false,"given":"Sodiq","family":"Fakorede","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Rehabilitation Science, and Athletic Training, University of Kansas Medical Center, Kansas City, KS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1730-4604","authenticated-orcid":false,"given":"Nike","family":"Idowu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,2,16]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104511"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1037\/a0029857"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-018-0107-y"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2024.101273"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24043754"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcmed.2012.11.009"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-024-00940-4"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2010.11.032"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac143"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13859"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16939"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4593"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1080\/17460441.2023.2277350"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-824467-8.00001-2"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt125"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00023.2009"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.11.049"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/s43141-021-00120-7"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e17026"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.01151-22"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fbinf.2024.1411935"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-013-9644-8"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.5b00864"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25071609"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmgm.2016.07.005"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/7934442"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.2174\/0115680266259174231006070637"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106631"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2023.1279740"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2015.07.018"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(00)00129-0"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm901137j"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11030-023-10689-5"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/1758-2946-1-8"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.200700139"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm101421d"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty707"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.104.000794"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1021\/ci200317s"},{"key":"e_1_3_4_42_2","first-page":"598728","article-title":"Computational insights into substrate and site specificities, catalytic mechanism, and protonation states of the catalytic asp dyad of \u03b2-secretase","volume":"2014","author":"Barman A","year":"2014","unstructured":"Barman A, Prabhakar R. Computational insights into substrate and site specificities, catalytic mechanism, and protonation states of the catalytic asp dyad of \u03b2-secretase. Scientifica (Cairo) 2014; 2014: 598728.","journal-title":"Scientifica (Cairo)"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11152412"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molliq.2022.118901"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12478"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.2016.1121815"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2016.07.005"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877241313049","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/13872877241313049","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877241313049","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:09:39Z","timestamp":1777370979000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/13872877241313049"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":46,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1177\/13872877241313049"],"URL":"https:\/\/doi.org\/10.1177\/13872877241313049","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2]]}}}