{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T15:22:30Z","timestamp":1771341750263,"version":"3.50.1"},"reference-count":51,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82471273"],"award-info":[{"award-number":["82471273"]}]},{"name":"National Natural Science Foundation of China","award":["81901303"],"award-info":[{"award-number":["81901303"]}]},{"name":"National Natural Science Foundation of China","award":["82301621"],"award-info":[{"award-number":["82301621"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron degeneration and \u03b1-synuclein (\u03b1-syn) aggregation. Lipid metabolism dysfunction may contribute to PD progression. This study aims to identify lipid metabolism-related genes (LMGs) associated with PD using an integrative transcriptomic analysis of microarray and single-cell RNA sequencing (scRNA-seq) datasets from patients with PD and healthy controls. Differentially expressed genes (DEGs) related to lipid metabolism were identified, and key genes were further filtered using weighted gene co-expression network analysis (WGCNA) and machine learning algorithms. Four LMGs, AGPAT2, ASAH2, FA2H, and MECR were identified, with MECR being notably downregulated in both bulk and single-cell transcriptomic analyses of PD patients. This downregulation was further validated in \u03b1-syn PFF-induced PD models. Virtual screening and molecular simulations identified potential allosteric modulators of MECR, which may offer a pathway for future therapeutic exploration. This study highlights MECR as a critical gene link between lipid metabolism dysfunction and PD, suggesting the need for further investigation into its therapeutic implications.<\/jats:p>","DOI":"10.3390\/ijms26020550","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T06:25:54Z","timestamp":1736490354000},"page":"550","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification of Downregulated MECR Gene in Parkinson\u2019s Disease Through Integrated Transcriptomic Analysis and Validation"],"prefix":"10.3390","volume":"26","author":[{"given":"Danlei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haoheng","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"An","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongming","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of General Practice, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijuan","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongjie","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of General Practice, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0896-6273(03)00568-3","article-title":"Parkinson\u2019s disease: Mechanisms and models","volume":"39","author":"Dauer","year":"2003","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S0140-6736(14)61393-3","article-title":"Parkinson\u2019s disease","volume":"386","author":"Kalia","year":"2015","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1194\/jlr.E400004-JLR200","article-title":"A comprehensive classification system for lipids","volume":"46","author":"Fahy","year":"2005","journal-title":"J. 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