AUTHOR=Liu Xiaolan , Lu Baili , Huang Hui 

TITLE=Investigation of the shared biological mechanisms and common biomarker APTAF1 of sleep deprivation and mild cognitive impairment using integrated bioinformatics analysis

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1387569

DOI=10.3389/fphar.2024.1387569

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold> The relationship between sleep loss and cognitive impairment has long been widely recognized, but there is still a lack of complete understanding of the underlying mechanisms and potential biomarkers. The purpose of this study is to further explore the shared biological mechanisms and common biomarkers between sleep loss and cognitive impairment.</p><p><bold>Methods:</bold> The mitochondria-related genes and gene expression data were downloaded from the MitoCarta3.0 and Gene Expression Omnibus (GEO) databases. We identified the differentially expressed mitochondrial-related genes by combing the differentially expressed genes (DEGs) in sleep deprivation (SD) and mild cognitive impairment (MCI) datasets with mitochondria-related gene lists. Shared DEGs were then further analyzed for enrichment analysis. Next, the common biomarker was identified using two machine learning techniques and further validated using two independent GEO datasets. Then GSEA and GSVA were conducted to analyze the functional categories and pathways enriched for the common biomarker. Finally, immune infiltration analysis was used to investigate the correlation of immune cell infiltration with the common biomarker in SD and MCI.</p><p><bold>Results:</bold> A total of 32 mitochondrial-related differentially expressed genes were identified in SD and MCI. GO analysis indicated that these genes were significantly enriched for mitochondrial transport, and KEGG analysis showed they were mainly involved in pathways of neurodegenerative diseases. In addition, ATPAF1, which was significantly down-regulated in both SD and MCI, was identified through machine learning algorithms as the common biomarker with favorable diagnostic performance. GSEA and GSVA revealed that ATPAF1 was mainly involved in metabolic pathways, such as oxidative phosphorylation, acetylcholine metabolic process, valine, leucine and isoleucine degradation. Immune infiltration analysis showed that the expression of ATPAF1 was correlated with changes in immune cells, especially those key immune cell types associated with SD and MCI.</p><p><bold>Discussion:</bold> This study firstly revealed that mitochondrial dysfunction may be the common pathogenesis of sleep loss and mild cognitive impairment and identified ATPAF1 as a possible biomarker and therapeutic target involved in SD and MCI.</p>