title: Pathways to decoding the clinical potential of stress response FOXO-interaction networks for Huntington's disease: of gene prioritization and context dependence.
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.
authors.affiliation: Laboratory of Neuronal Cell biology and Pathology, INSERM Unit 894, CNRS UMR 7102, University Pierre and Marie Curie Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Parmentier
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Lejeune
authors.forename: Christian
authors.initials: C
authors.lastname: Neri
keywords: FOXO network; Huntington's disease; cellular-stress response; clinical potential; entropy; gene prioritization; system-level approach