{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:03:10Z","timestamp":1791259390129,"version":"4.1.0"},"reference-count":99,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Traumatic brain injury (TBI) can generally be divided into focal damage and diffuse damage, and neonate Hypoxia-Ischemia Brain Damage (nHIBD) is one of the causes of diffuse damage. Patients with nHIBD are at an increased risk of developing Alzheimer\u2019s disease (AD). However, the shared pathogenesis of patients affected with both neurological disorders has not been fully elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Purpose<\/jats:title><jats:p>We here aim to identify the shared molecular signatures between nHIBD and AD. We used an integrated analysis of the cortex gene expression data, targeting differential expression of genes related to the mechanisms of neurodegeneration and cognitive impairment following traumatic brain injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The gene expression profiles of Alzheimer\u2019s disease (GSE203206) and that of Neonate Hypoxia-Ischemia Brain Damage (GSE23317) were obtained from the Gene Expression Omnibus (GEO) database. After identifying the common differentially expressed genes (DEGs) of Alzheimer\u2019s disease and neonate Hypoxia-Ischemia Brain Damage by limma package analysis, five kinds of analyses were performed on them, namely Gene Ontology (GO) and pathway enrichment analysis, protein\u2013protein interaction network, DEG-transcription factor interactions and DEG-microRNA interactions, protein-drug interactions and protein-disease association analysis, and gene-inflammation association analysis and protein-inflammation association analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 12 common DEGs were identified including HSPB1, VIM, MVD, TUBB4A, AACS, ANXA6, DIRAS2, RPH3A, CEND1, KALM, THOP1, AREL1. We also identified 11 hub proteins, three central regulatory transcription factors, and three microRNAs encoded by the DEGs. Protein-drug interaction analysis showed that CYC1 and UQCRFS1 are associated with different drugs. Gene-disease association analysis shows Mammary Neoplasms, Neoplasm Metastasis, Schizophrenia, and Brain Ischemia diseases are the most relevant to the hub proteins we identified. Gene-inflammation association analysis shows that the hub gene AREL1 is related to inflammatory response, while the protein-inflammation association analysis shows that the hub proteins AKT1 and MAPK14 are related to inflammatory response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study provides new insights into the shared molecular mechanisms between AD and nHIBD. These common pathways and hub genes could potentially be used to design therapeutic interventions, reducing the likelihood of Alzheimer\u2019s disease development in survivors of neonatal Hypoxic-Ischemia brain injury.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2024.1511668","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T06:12:04Z","timestamp":1736748724000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Neuroinflammation mediates the progression of neonate hypoxia-ischemia brain damage to Alzheimer\u2019s disease: a bioinformatics and experimental study"],"prefix":"10.3389","volume":"16","author":[{"given":"Shengjie","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruqiu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoqin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"868","DOI":"10.2174\/1389200218666170728115606","article-title":"Translational shift of HSP90 as a novel therapeutic target from cancer to neurodegenerative disorders: an emerging trend in the cure of Alzheimer\u2019s and Parkinson\u2019s diseases","volume":"18","author":"Alam","year":"2017","journal-title":"Curr. 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