{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T20:11:08Z","timestamp":1783368668713,"version":"3.54.6"},"reference-count":78,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":20,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah bint Abdulrahman University","doi-asserted-by":"publisher","award":["PNURSP2025R110"],"award-info":[{"award-number":["PNURSP2025R110"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic relapsing colonic inflammation, specifically ulcerative colitis (UC), causes persistent mucosal injury and disrupts the gut\u2013brain axis. This disruption leads to basal ganglia neuroinflammation and ultimately extrapyramidal motor dysfunction. Dysregulation of the Dectin 1\/leucine-rich repeat kinase 2 (LRRK2)\/\u03b1-synuclein (\u03b1Syn) signaling exacerbates inflammation. This study investigated whether modulation of this pathway affects UC progression and is associated with motor deficits using trimetazidine (TMZ) treatment in a Bagg albino c (BALB\/c) mice model. Furthermore, we examined the role of this pathway through molecular docking followed by molecular dynamics simulations to evaluate the plausibility of TMZ interactions with Dectin-1, LRRK2, and \u03b1-syn proteins. Our results indicate that TMZ improved behavioral changes and also significantly reduced serum interferone-\u03b3 (IFN-\u03b3) and NF-kB levels, along with decreased Dectin-1, LRRK2, and \u03b1Syn expression. TMZ also mitigated colonic inflammation, as shown by reducing fecal calprotectin and fecal occult blood, supported by histological examinations. Furthermore, TMZ restored autophagic flux by reducing P62 accumulation and enhancing LAMP2 expression. Molecular docking and dynamics confirmed TMZ binding to Dectin-1, LRRK2, and \u03b1Syn, through hydrophobic and hydrophilic interactions. These findings suggest a potential molecular basis for the observed associations between the Dectin-1\/LRRK2\/\u03b1-synuclein axis and UC-related motor dysfunction, warranting further experimental validation, establishing TMZ's therapeutic potential for managing colonic inflammation and associated neurological manifestations.<\/jats:p>","DOI":"10.1093\/mam\/ozaf118","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T13:25:20Z","timestamp":1764768320000},"source":"Crossref","is-referenced-by-count":2,"title":["Trimetazidine Attenuates Ulcerative Colitis-Linked Extrapyramidal Dysfunction by Mediated Dectin-1\/LRRK2\/\u03b1-Synuclein Autophagy Axis"],"prefix":"10.1093","volume":"32","author":[{"given":"Shaimaa H","family":"Mahmoud","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Ain Shams University , Cairo 11591 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameeah Mejbel Hamad","family":"Algenabi","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, College of Medicine, University of Anbar , Anbar, Ramadi City 55431 ,","place":["Iraq"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6077-4214","authenticated-orcid":false,"given":"Anwar","family":"Nather Seiwan","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, University of Basrah , Basrah 61004 ,","place":["Iraq"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8199-2512","authenticated-orcid":false,"given":"Dalia","family":"Alaa El-Din Aly El-Waseef","sequence":"additional","affiliation":[{"name":"Department of Histology and Cell Biology, Faculty of Medicine, Ain Shams University , Cairo 11591 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omnyah A","family":"El-Kharashi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Ain Shams University , Cairo 11591 ,","place":["Egypt"]},{"name":"Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Misr University for Science and Technology , Cairo 77 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa M","family":"Elshaer","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Ain Shams University , Cairo 11591 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emad R","family":"Sindi","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, University of Jeddah , Jeddah 23890 ,","place":["Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahani Mohamed Ibrahim","family":"Al-Hazani","sequence":"additional","affiliation":[{"name":"Biology Department, College of Science and Humanities, Prince Sattam bin Abdulaziz University , Al-Kharj 16273 ,","place":["Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samar F","family":"Ezzat","sequence":"additional","affiliation":[{"name":"Department of Histology and Cell Biology, Faculty of Medicine, Ain Shams University , Cairo 11591 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Essmat","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Al Azhar University , Cairo 11651 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyfa A","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Department of Biology Faculty of Science, Al-Baha University , Alaqiq 65779-7738 ,","place":["Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fawzyah Obeedallah","family":"Albaldi","sequence":"additional","affiliation":[{"name":"Department of Biology Faculty of Science, Al-Baha University , Alaqiq 65779-7738 ,","place":["Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal F","family":"Dawood","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Princess Nourah bint Abdulrahman University , P.O. 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