Analysis of the potential regulatory mechanism of PIEZO1 in Alzheimer’s disease based on RNA sequencing

Abstract

The ion channel protein PIEZO1 regulates complex processes in Alzheimer’s disease (AD). This study explored the regulatory mechanism of PIEZO1 in AD using bioinformatic analysis, aiming to identify AD-associated genes and potential therapeutic strategies. RNA sequencing (RNA-seq) data based on an in vitro model of AD were obtained from the Gene Expression Omnibus (GEO) database, and differential expression analysis was performed using the DESeq2 R package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted on the identified differentially expressed genes (DEGs). Gene set enrichment analysis (GSEA) and principal component analysis (PCA) were also performed on the gene expression data. PCA clustering revealed overall significant differences among the three groups of samples (control, AD, and PF-562271 intervention group). All DEGs in the three sample groups were subjected to k-means hierarchical clustering, revealing four clusters. The matrix antigen plot indicated multiple changes in the average millions of fragments per thousand bases value of each gene among the groups. Functional annotation was performed for the DEGs between the two groups, and GSEA identified both activated and inhibited pathways, distinguishing the groups. Notably, the expression of PIEZO1 was higher in the AD group than in the control group. This study confirmed elevated PIEZO1 expression in astrocyte AD models, which is associated with the regulation of the extracellular matrix, cell–substrate adhesion, synaptic migration, and other related functions and pathways.