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- W2252384906 endingPage "130" @default.
- W2252384906 startingPage "117" @default.
- W2252384906 abstract "Huntington's disease is a progressive neurodegenerative disorder characterized by motor disturbances, cognitive decline, and neuropsychiatric symptoms. In this study, we utilized network-based analysis in an attempt to explore and understand the underlying molecular mechanism and to identify critical molecular players of this disease condition. Using human post-mortem microarrays from three brain regions (cerebellum, frontal cortex and caudate nucleus) we selected in a four-step procedure a seed set of highly modulated genes. Several protein-protein interaction networks, as well as microRNA-mRNA networks were constructed for these gene sets with the Elsevier Pathway Studio software and its associated ResNet database. We applied a gene prioritizing procedure based on vital network topological measures, such as high node connectivity and centrality. Adding to these criteria the guilt-by-association rule and exploring their innate biomolecular functions, we propose 19 novel genes from the analyzed microarrays, from which CEBPA, CDK1, CX3CL1, EGR1, E2F1, ERBB2, LRP1, HSP90AA1 and ZNF148 might be of particular interest for experimental validation. A possibility is discussed for dual-level gene regulation by both transcription factors and microRNAs in Huntington's disease mechanism. We propose several possible scenarios for experimental studies initiated via the extra-cellular ligands TGFB1, FGF2 and TNF aiming at restoring the cellular homeostasis in Huntington's disease." @default.
- W2252384906 created "2016-06-24" @default.
- W2252384906 creator A5017568569 @default.
- W2252384906 creator A5044573961 @default.
- W2252384906 date "2016-01-01" @default.
- W2252384906 modified "2023-10-14" @default.
- W2252384906 title "Network analysis of human post-mortem microarrays reveals novel genes, microRNAs, and mechanistic scenarios of potential importance in fighting huntington's disease" @default.
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