{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T07:44:30Z","timestamp":1773733470863,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T00:00:00Z","timestamp":1773532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SIP High-Quality Innovation Platform for Chronic Diseases","award":["YZCXPT2022203"],"award-info":[{"award-number":["YZCXPT2022203"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82273768"],"award-info":[{"award-number":["82273768"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82574254"],"award-info":[{"award-number":["82574254"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Psoriasis, a chronic inflammatory skin disease, is driven by immune dysregulation and keratinocyte hyperproliferation, with current biologics facing limitations. Emerging evidence points to mitochondrial dysfunction and a pathological shift to aerobic glycolysis as core disease drivers. Here, we report that MitoFu-O, a novel mitochondria-targeting TPP-thiazole derivative, effectively ameliorates psoriasiform inflammation in imiquimod-induced mice and cytokine-stimulated keratinocytes. Mechanistically, MitoFu-O acts by inhibiting pathological glycolysis, downregulating key glycolytic enzymes (HK1, GAPDH, LDHA), and subsequently suppressing the activation of pivotal pro-inflammatory signaling pathways (MAPK, NF-\u03baB, and STAT3). Our findings establish targeted mitochondrial modulation as a potent therapeutic strategy, positioning MitoFu-O as a promising lead compound that acts upstream of cytokine signaling by normalizing the metabolic reprogramming fundamental to psoriatic pathogenesis.<\/jats:p>","DOI":"10.3390\/molecules31060982","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T14:30:32Z","timestamp":1773671432000},"page":"982","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TPP-Thiazole Derivatives Ameliorate Psoriasiform Inflammation by Glycolysis Inhibition"],"prefix":"10.3390","volume":"31","author":[{"given":"Xinwei","family":"Meng","sequence":"first","affiliation":[{"name":"Wisdom Lake Academy of Pharmacy, Xi\u2019an Jiao Tong Liverpool University, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ci-An","family":"Cheng","sequence":"additional","affiliation":[{"name":"Wisdom Lake Academy of Pharmacy, Xi\u2019an Jiao Tong Liverpool University, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhirui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Wisdom Lake Academy of Pharmacy, Xi\u2019an Jiao Tong Liverpool University, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siying","family":"Qu","sequence":"additional","affiliation":[{"name":"Wisdom Lake Academy of Pharmacy, Xi\u2019an Jiao Tong Liverpool University, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Wisdom Lake Academy of Pharmacy, Xi\u2019an Jiao Tong Liverpool University, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1342-756X","authenticated-orcid":false,"given":"Jinxin","family":"Gu","sequence":"additional","affiliation":[{"name":"Wisdom Lake Academy of Pharmacy, Xi\u2019an Jiao Tong Liverpool University, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Wisdom Lake Academy of Pharmacy, Xi\u2019an Jiao Tong Liverpool University, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keyue","family":"Ding","sequence":"additional","affiliation":[{"name":"Wisdom Lake Academy of Pharmacy, Xi\u2019an Jiao Tong Liverpool University, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0802-6446","authenticated-orcid":false,"given":"Lei","family":"Fu","sequence":"additional","affiliation":[{"name":"Wisdom Lake Academy of Pharmacy, Xi\u2019an Jiao Tong Liverpool University, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0947-2712","authenticated-orcid":false,"given":"Mengchen","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, College of Pharmaceutical Sciences, Soochow University Medical College, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daiyun","family":"Huang","sequence":"additional","affiliation":[{"name":"Wisdom Lake Academy of Pharmacy, Xi\u2019an Jiao Tong Liverpool University, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixue","family":"Qiao","sequence":"additional","affiliation":[{"name":"Wisdom Lake Academy of Pharmacy, Xi\u2019an Jiao Tong Liverpool University, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/S0140-6736(20)32549-6","article-title":"Psoriasis","volume":"397","author":"Griffiths","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1016\/j.jid.2024.05.015","article-title":"Paradoxical Psoriasis: An Updated Review of Clinical Features, Pathogenesis, and Treatment Options","volume":"144","author":"Maronese","year":"2024","journal-title":"J. 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