چکیده (انگلیسی):

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 fromthree brain regions (cerebellum, frontal cortex and
caudate nucleus) we selected in a four-step procedure a seed set of highlymodulated 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.
© 2016 Chandrasekaran, Bonchev. Published by Elsevier B.V. on behalf of the Research Network of Computational
and Structural Biotechnology. This is an open access article under the CC BY license