The mechanism of mitochondrial metabolic gene PMAIP1 involved in Alzheimer's disease process based on bioinformatics analysis and experimental validation

Highlights

• PMAIP1 may be a potential biomarker for Alzheimer's Disease.

• PMAIP1 has a certain pro-apoptotic effect.

• PMAIP1 is participate in hippocampal neuron damage by regulating mitochondrial function.

Abstract

Objectives

This study explored novel biomarkers that can affect the diagnosis and treatment in Alzheimer's Disease (AD) related to mitochondrial metabolism.

Methods

The authors obtained the brain tissue datasets for AD from the Gene Expression Omnibus (GEO) and downloaded the mitochondrial metabolism-related genes set from MitoCarta 3.0 for analysis. Differentially Expressed Genes (DEGs) were screened using the “limma” R package, and the biological functions and pathways were investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The LASSO algorithm was used to identify the candidate center genes and validated in the GSE97760 dataset. PMAIP1 with the highest diagnostic value was selected and its effect on the occurrence of AD by biological experiments.

Results

A sum of 364 DEGs and 50 hub genes were ascertained. GO and KEGG enrichment analysis demonstrated that DEGs were preponderantly associated with cell metabolism and apoptosis. Five genes most associated with AD as candidate central genes by LASSO algorithm analysis. Then, the expression level and specificity of candidate central genes were verified by GSE97760 dataset, which confirmed that PMAIP1 had a high diagnostic value. Finally, the regulatory effects of PMAIP1 on apoptosis and mitochondrial function were detected by siRNA, flow cytometry and Western blot. siRNA-PMAIP1 can alleviate mitochondrial dysfunction and inhibit cell apoptosis.

Conclusion

This study identified biomarkers related to mitochondrial metabolism in AD and provided a theoretical basis for the diagnosis of AD. PMAIP1 was a potential candidate gene that may affect mitochondrial function in Hippocampal neuronal cells, and its mechanism deserves further study.

Keywords
Alzheimer's disease; Apoptosis; Biomarkers; Mitochondrial Metabolism