Identification of Key Regulatory Genes and Pathways in Prefrontal Cortex of Alzheimer ’s Disease

This study aims to identify the potential therapeutic target genes and related pathways in PFC of AD. First, differential expression analyses were performed on transcriptome microarray of PFC between AD specimens and non-AD controls. Second, protein–protein interaction net works were constructed based on the identified differentially expressed genes to explore candidate therapeutic target genes. Finally, these candidate genes were validated through biological experiments. The enrichment analyses showed that the differentially expressed genes were significantly enriche d in protein functions and pathways related to AD. Furthermore, the top ten hub genes in the protein–protein interaction network (ELAVL1, CUL3, MAPK6, FBXW11, YWHAE, YWHAZ, GRB2, CLTC, YWHAQ, and PDHA1) were proved to be directly or indirectly related to AD. Besides, six genes (PDHA1, CLTC, YWHAE, MAPK6, YWHAZ, and GRB2) of which were validated to significantly altered in AD mice by biological experiments. Importantly, the most significantly changed gene, PDHA1, was proposed for the first time that may be serve as a target gene in AD treatment. In summary, several genes and pathways that pla y critical roles in PFC of AD patients have been uncovered, which will provide novel insights on molecular targets for treatment and diagnostic biomarkers of AD.
Source: Interdisciplinary Sciences, Computational Life Sciences - Category: Bioinformatics Source Type: research