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During Alzheimer's disease (AD), ERK1 phosphorylates tau at 15 phosphorylation sites, leading to the formation of neurofibrillary tangles. The overactivation of ERK1 in microglia promotes the release of pro-inflammatory cytokines, which results in neuroinflammation. Additionally, elevated oxidative stress during AD stimulates the ERK1 pathway, leading to neuronal loss.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Because ERK1 signaling plays a significant role in tau phosphorylation, targeting ERK1 may be therapeutically beneficial by either preventing excessive activation of the signaling pathway or altering its pathway to enhance neuroprotective effects during AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study employed structure-based virtual screening of phytoconstituents from the IMPPAT library. Subsequently, in-depth docking and molecular dynamics (MD) simulation studies were implemented to identify potential ERK1 inhibitors with desirable pharmacological properties.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Silandrin and Hydroxytuberosone were found to be potential ERK1 inhibitors with higher affinity and specificity than the control molecule Tizaterkib. These compounds specifically bind to the ERK1 substrate binding pocket and interact with crucial residues. Finally, the elucidated compounds with ERK1 were evaluated using an all-atom molecular MD simulation to analyze structural dynamics, structural compactness, hydrogen bond dynamics, principal component analysis, and free energy landscape.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The study suggested that Silandrin and Hydroxytuberosone can further be exploited as potential lead molecules for therapeutic development against ERK1-mediated AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877241309592","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T20:35:56Z","timestamp":1736973356000},"page":"1226-1244","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Discovering potential ERK1 inhibitors from natural products for therapeutic targeting of Alzheimer's disease"],"prefix":"10.1177","volume":"103","author":[{"given":"Mohammad","family":"Taufeeq","sequence":"first","affiliation":[{"name":"Department of Computer Science, Jamia Millia Islamia, New Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arunabh","family":"Choudhury","sequence":"additional","affiliation":[{"name":"Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9769-2557","authenticated-orcid":false,"given":"Afzal","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3044-1267","authenticated-orcid":false,"given":"Mohamed F","family":"Alajmi","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0399-4835","authenticated-orcid":false,"given":"Taj","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7055-7056","authenticated-orcid":false,"given":"Anas","family":"Shamsi","sequence":"additional","affiliation":[{"name":"Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3663-4940","authenticated-orcid":false,"given":"Md Imtaiyaz","family":"Hassan","sequence":"additional","affiliation":[{"name":"Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/1556-4029.13885"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102476"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1717-7"},{"key":"e_1_3_5_5_2","volume-title":"World Alzheimer Report 2018. 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