P3‐085: Interaction network of tau protein, beta‐amyloid protein, and amyloid protein precursor under oxidative stress in Alzheimer's disease

MicroRNAs are post-transcriptional gene expression regulators. Currently, together with a set of proteins, they have been studied for their possible involvement with oxidative stress and as possible biomarkers for Alzheimer's disease (AD), one of the most common causes of dementia. The goal of this project is to correlate the presence of Tau Tangles and Amyloid Deposits to oxidative stress and amyloid protein precursor, in an attempt to capture the essence of such mechanisms that are related to AD. A systematic literature review was conducted using PubMed, Web of science and Scopus databases. Three researches were conducted, using the Mesh terms “microRNA, miRNA, Alzheimer's Disease and Oxidative Stress” in common. Each research received one of three Mesh proteins “Tau, Amyloid or Amyloid Protein Precursor. Our study selected 2 articles for data extraction among the 34 found. The Mirbase was used to verify the authenticity of the mature miRNA. The DIANA database was used to establish miRNA and gene interaction which considered only miTG data with scores over or equivalent to 0.999999. Finally, we created a protein-protein interaction network using Cytoscape. We identified 7 differentially expressed miRNAs with p-value below 5% and fold-change greater than 1.5. The DIANA database identified 75 genes related to 7 miRNAs with miTG scores over or equivalent to 0.999999. The Protein-Protein network, constructed from the 75 genes, identified important pathways related to the regulation of carbohydrate biosynthetic process (Figure 1), negative regulation of translation involved in gene miRNA silencing (Figure 2), SMAD binding (Figure 3), carbon-oxygen lyase (Figure 3), mRNA binding (Figure 2), RNA polymerase II core promoter proximal region sequence and specific DNA binding transcription factor activity involved in negative regulation of transcription (Figure 4). The selected MicroRNAs interact with genes that are important in the regulation of several Mitochondrial mechanisms, such as enzymatic proteins and intracellular signaling which are important for mitochondrial activity and cellular growth (Figure 5). In addition, genes found to be related to mutational fix, miRNA production and transcription factors have influence in mutations and mitochondrial dysfunction, which may lead to oxidative stress and protein malfunction.