AUTHOR=Parmentier Frederic , Lejeune Francois-Xavier , Neri Christian TITLE=Pathways to decoding the clinical potential of stress response FOXO-interaction networks for Huntington's disease: of gene prioritization and context dependence JOURNAL=Frontiers in Aging Neuroscience VOLUME=5 YEAR=2013 URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2013.00022 DOI=10.3389/fnagi.2013.00022 ISSN=1663-4365 ABSTRACT=

The FOXO family of transcription factors is central to the regulation of organismal longevity and cellular survival. Several studies have indicated that FOXO factors lie at the center of a complex network of upstream pathways, cofactors and downstream targets (FOXO-interaction networks), which may have developmental and post-developmental roles in the regulation of chronic-stress response in normal and diseased cells. Noticeably, FOXO factors are important for the regulation of proteotoxicity and neuron survival in several models of neurodegenerative disease, suggesting that FOXO-interaction networks may have therapeutic potential. However, the status of FOXO-interaction networks in neurodegenerative disease remains largely unknown. Systems modeling is anticipated to provide a comprehensive assessment of this question. In particular, interrogating the context-dependent variability of FOXO-interaction networks could predict the clinical potential of cellular-stress response genes and aging regulators for tackling brain and peripheral pathology in neurodegenerative disease. Using published transcriptomic data obtained from murine models of Huntington's disease (HD) and post-mortem brains, blood samples and induced-pluripotent-stem cells from HD carriers as a case example, this review briefly highlights how the biological status and clinical potential of FOXO-interaction networks for HD may be decoded by developing network and entropy based feature selection across heterogeneous datasets.