O2-13-06: The protein-protein interaction network analysis of neurobiology of Alzheimer's disease: A blood-based mirna systematic revision study

Alzheimers & Dementia(2015)

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Abstract
microRNA are small, non-coding RNA that is involved in the regulation of mRNA activity. Abnormalities in microRNA expression has been involved in the physiopathology of Alzheimer's Disease (AD). The aim of this study is to carry out a systematic review of the literature to identify the microRNA that are abnormally expressed in AD subjects and to evaluate the genes and biological pathways that are regulated by these microRNAs. Systematic review of the literature was conducted using PubMed, Web of science and Scopus databases using the MeSH terms “microRNA, miRNA and Alzheimer's Disease”. We also made use of a GEO database for unpublished data. We identified 416 articles, and 6 were selected for data extraction. The verification of mature microRNAs authenticity used the Mirbase data bank. The establishment of miRNA and gene interaction with DIANA database considered was only miTG data with scores over or equivalent to 0.999999. Finally, we created a protein-protein interaction (PPI) network using Cytoscape program. We identified 77 differentially expressed miRNAs with p-value below 5% and fold-change greater than 1.5. The top 10 miRNAs with the biggest fold-change values built a successful Protein-Protein interaction network. The interaction with the group of 10 miRNAs selected identified were the result 447 genes (Figure 1) with a miTG score over or equivalent to 0.999999. The Protein-Protein network, constructed from the 447 genes, identified important pathways related to cellular aging, neuroglia cell development, regulation of precursor proteins for beta-amyloid, tau protein regulation, oxidative stress, leukocytes regulation, neuron cellular morphogenesis, MAPK cascade, negative regulation of gene expression, regulation of translation and angiogenesis (Figures 2, 3 and 4). The Protein-protein network. Some methabolic pathways of the genes related to the miRNas found. Importante pathways such as MAPK cascade, negative regulation of gene expression and regulation of translation Importante pathways such as central nervous system neuron development, morphogenesis, regulation of carbohydrate and regulation of glucose transport. The present data indicates that abnormalities in miRNAs expression have an important role in the pathogenesis of AD. The identification of a miRNA plasma profile may aid the identification of subjects at increased risk of developing AD and novel targets for the development of drugs with potential disease-modifying effects to prevent or delay the progression of AD.
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Key words
alzheimer disease,neurobiology,mirna,protein-protein,blood-based
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