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.
Highlights
In 1872, a young American physician named George Huntington was the first to recognize a specific inherited neurodegenerative disorder
One of the major conclusions of this study was that the differential gene expression in Huntington's disease (HD) brains showed distinct regional pattern similar to an already known pattern of neuronal loss
We found in the direct interaction network 26 genes that have already been associated to Huntington's disease
Summary
In 1872, a young American physician named George Huntington was the first to recognize a specific inherited neurodegenerative disorder. Later it was named after him as Huntington's disease (HD) and in early 1990s the mutant gene Huntingtin (HTT) was discovered to be the cause of the disease. Expansion of 36 or more CAG trinucleotide (polyQ) repeats in HTT gene is the hallmark characteristic of the disease. PolyQ expanded HTT is considered as a trigger of the neurodegeneration that eventually caused all the Huntington's disease symptoms. The disease is described by progressive motor, cognitive as well as emotional disturbances. The motor symptoms include chorea, dystonia, rigidity, postural instability, etc. Depression and personality changes are the major emotional disturbances part of the disorder. Like Alzheimer's disease (AD), short-term memory loss, confusion and disorientation are some of the cognitive issues found in HD patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Computational and Structural Biotechnology Journal
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
