The most predominant form of dementia is Alzheimer’s disease (AD), which most often manifests as loss of cognitive ability and episodic memory. Repressor element-1 silencing transcription factor (REST), generally referred to as neuron-restrictive silencer factor, is a transcriptional repressor that is typically expressed throughout embryogenesis and is essential for regulating the genes that are unique to neurons. The genes modulating neurotransmitter synthetases, synaptic vesicle proteins, transporters, receptors, and various ion channels in the central nervous system are regulated by REST. In neurons from the hippocampus and prefrontal cortical regions, there was a discernible decline in the nuclear REST level in AD patients. Despite the importance of REST, very little is known regarding the regulatory mechanism of REST. In this study, we have computationally explored the role of REST in differential expression of genes in AD by the construction of gene/protein interaction networks. In addition, we have also investigated the interaction between REST and other transcription factors (TFs) in the regulation of genes. When the gene expression data of AD samples were compared with the control samples, 97,457 genes from the 850,125 total examined genes displayed differential expression. 33 genes among the DEGs regulated REST, while 364 genes were controlled by REST. Twenty important TFs were discovered to be directly involved in the REST regulation among the DEGs. In addition, among the DEGs, 17 TFs were found to share common targets with REST that are involved in AD. Gene annotation analysis has shown that REST along with other TFs regulated genes that are involved in processes such as synaptic signaling, neuronal death, metabolic processes etc. The results demonstrated the critical regulatory role of REST in AD pathogenesis.
Key words: Differentially expressed genes, Protein-Protein interactions, Network analysis, Regulatory clusters, Hub proteins.
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