{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:58:47Z","timestamp":1790812727052,"version":"4.1.0"},"reference-count":85,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T00:00:00Z","timestamp":1642377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018749","name":"Korea Brain Research Institute","doi-asserted-by":"publisher","award":["21-BR-02-08"],"award-info":[{"award-number":["21-BR-02-08"]}],"id":[{"id":"10.13039\/100018749","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003715","name":"Korea Research Institute of Bioscience and Biotechnology","doi-asserted-by":"publisher","award":["KGM4562121"],"award-info":[{"award-number":["KGM4562121"]}],"id":[{"id":"10.13039\/501100003715","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Insulin in the brain is a well-known critical factor in neuro-development and regulation of adult neurogenesis in the hippocampus. The abnormality of brain insulin signaling is associated with the aging process and altered brain plasticity, and could promote neurodegeneration in the late stage of Alzheimer\u2019s disease (AD). The precise molecular mechanism of the relationship between insulin resistance and AD remains unclear. The development of phosphoproteomics has advanced our knowledge of phosphorylation-mediated signaling networks and could elucidate the molecular mechanisms of certain pathological conditions. Here, we applied a reliable phosphoproteomic approach to Neuro2a (N2a) cells to identify their molecular features under two different insulin-resistant conditions with clinical relevance: inflammation and dyslipidemia. Despite significant difference in overall phosphoproteome profiles, we found molecular signatures and biological pathways in common between two insulin-resistant conditions. These include the integrin and adenosine monophosphate-activated protein kinase pathways, and we further verified these molecular targets by subsequent biochemical analysis. Among them, the phosphorylation levels of acetyl-CoA carboxylase and Src were reduced in the brain from rodent AD model 5xFAD mice. This study provides new molecular signatures for insulin resistance in N2a cells and possible links between the molecular features of insulin resistance and AD.<\/jats:p>","DOI":"10.3390\/ijms23021006","type":"journal-article","created":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T20:46:03Z","timestamp":1642452363000},"page":"1006","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Comparative Phosphoproteomics of Neuro-2a Cells under Insulin Resistance Reveals New Molecular Signatures of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"23","author":[{"given":"Dayea","family":"Kim","sequence":"first","affiliation":[{"name":"New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDI hub), Daegu 41061, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeon Suk","family":"Jo","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases Research Group, Korea Brain Research Institute, Daegu 41062, Korea"},{"name":"Department of Brain-Cognitive Science, Daegu-Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Seul","family":"Jo","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases Research Group, Korea Brain Research Institute, Daegu 41062, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungwon","family":"Bae","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases Research Group, Korea Brain Research Institute, Daegu 41062, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang Woo","family":"Kwon","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases Research Group, Korea Brain Research Institute, Daegu 41062, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Seok","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Brain-Cognitive Science, Daegu-Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4090-3832","authenticated-orcid":false,"given":"Jong Hyuk","family":"Yoon","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases Research Group, Korea Brain Research Institute, Daegu 41062, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.neurobiolaging.2021.05.011","article-title":"Brain energy metabolism and neurodegeneration: Hints from CSF lactate levels in dementias","volume":"105","author":"Bonomi","year":"2021","journal-title":"Neurobiol. 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