Detecting Common Pathways and Key Molecules of Neurodegenerative Diseases from the Topology of Molecular Networks.

Abstract

MotivationNeurodegenerative diseases (NDs), including amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, and Huntington's disease, occur as a result of neurodegenerative processes. Thus, it has been increasingly appreciated that many neurodegenerative conditions overlap at multiple levels. However, traditional clinicopathological correlation approaches to better classify a disease have met with limited success. Discovering this overlap offers hope for therapeutic advances that could ameliorate many ND simultaneously. In parallel, in the last decade, systems biology approaches have become a reliable choice in complex disease analysis for gaining more delicate biological insights and have enabled the comprehension of the higher order functions of the biological systems.ResultsToward this orientation, we developed a systems biology approach for the identification of common links and pathways of ND, based on well-established and novel topological and functional measures. For this purpose, a molecular pathway network was constructed, using molecular interactions and relations of four main neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease). Our analysis captured the overlapped subregions forming molecular subpathways fully enriched in these four NDs. Also, it exported molecules that act as bridges, hubs, and key players for neurodegeneration concerning either their topology or their functional role.ConclusionUnderstanding these common links and central topologies under the perspective of systems biology and network theory and greater insights are provided to uncover the complex neurodegeneration processes.