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ORIGINAL RESEARCH article

Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
Volume 16 - 2024 | doi: 10.3389/fnagi.2024.1511668
This article is part of the Research Topic Targeted Drug Delivery and Mode of Action of Small Molecules in Neuroinflammation View all articles

Neuroinflammation mediates the progression of neonate Hypoxia-Ischemia Brain Damage to Alzheimer's disease: A bioinformatics and experimental study

Provisionally accepted
Shengjie Zhang Shengjie Zhang 1Ruqiu Zhang Ruqiu Zhang 1*Zhaoqin Chen Zhaoqin Chen 1*Zihan Shao Zihan Shao 1*An Li An Li 1Fan Li Fan Li 2*Fang Huang Fang Huang 1*
  • 1 Yunnan University, Kunming, China
  • 2 Shantou University, Shantou, Guangdong Province, China

The final, formatted version of the article will be published soon.

    Background: 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's disease (AD).However, the shared pathogenesis of patients affected with both neurological disorders has not been fully elucidated.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. Methods: The gene expression profiles of Alzheimer's 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's 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-protein interaction network, DEG-transcription factor interactions and DEG-microRNA interactions, protein-drug interactions and protein-disease association analysis, and geneinflammation association analysis and protein-inflammation association analysis.Results: 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.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's disease development in survivors of neonatal Hypoxic-Ischemia brain injury.

    Keywords: Alzheimer's disease, neonate Hypoxia-Ischemia Brain Damage, Bioinformatics analysis, Neuroinflammation, Pathophysiological mechanisms

    Received: 16 Oct 2024; Accepted: 05 Dec 2024.

    Copyright: © 2024 Zhang, Zhang, Chen, Shao, Li, Li and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Ruqiu Zhang, Yunnan University, Kunming, China
    Zhaoqin Chen, Yunnan University, Kunming, China
    Zihan Shao, Yunnan University, Kunming, China
    Fan Li, Shantou University, Shantou, 515063, Guangdong Province, China
    Fang Huang, Yunnan University, Kunming, China

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