{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:29:27Z","timestamp":1792466967265,"version":"4.5.0"},"reference-count":55,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T00:00:00Z","timestamp":1729036800000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271275"],"award-info":[{"award-number":["82271275"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Insulin\u2010like growth factor binding protein 2 (IGFBP2) is implicated in various neurodegenerative diseases. However, its role in Parkinson's disease (PD) is unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>PD rat model was established by 6\u2010OHDA injection. After 3\u2009weeks, mRNA\u2010seq was conducted. Rats received rIGFBP2 via intra\u2010MFB injection 6\u2009h prior to 6\u2010OHDA infusion, and the effect of IGFBP2 in PD rats was investigated by western blotting, IHC, specific kits, JC\u20101 staining, and TUNEL analysis. In\u00a0vitro, PC12 cells were treated with 6\u2010OHDA, and CCK\u20108, specific kits, Hoechst 33258 staining, Western blotting, and JC\u20101 staining were performed to assess the IGFBP2's role.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>mRNA\u2010seq revealed DEGs in PD, with attention to downregulated IGFBP2. rIGFBP2 treatment aggravated neurobehavioral deficits, decreased TH expression, \u03a8m, ATP level and SOD, GSH\u2010Px activities but increased \u03b1\u2010synuclein, ROS, MDA, mitochondrial cytochrome <jats:italic>c<\/jats:italic> contents, cell apoptosis in 6\u2010OHDA\u2010lesioned rats, which might be mediated through inactivating IGF\u20101R\/AKT pathway. In 6\u2010OHDA\u2010treated PC12 cells, rIGFBP2 aggravated cell injury, demonstrated by decreased cell viability and increased apoptosis, oxidative stress, and mitochondrial dysfunction. Co\u2010treatment with rIGFBP2 and rIGF\u20101 partially reversed the effect of rIGFBP2 on cell damage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>IGFBP2 exacerbates neurodegeneration in PD through increasing oxidative stress, mitochondrial dysfunction, and apoptosis via inhibiting IGF\u20101R\/AKT pathway.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70076","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T12:40:12Z","timestamp":1729082412000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Insulin\u2010Like Growth Factor Binding Protein 2 Drives Neurodegeneration in Parkinson's Disease: Insights From In\u00a0Vivo and In\u00a0Vitro Studies"],"prefix":"10.1111","volume":"30","author":[{"given":"Jing","family":"An","sequence":"first","affiliation":[{"name":"Department of Neurology Shengjing Hospital of China Medical University  Shenyang Liaoning 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