title: Metabolism and epigenetics in the nervous system: Creating cellular fitness and resistance to neuronal death in neurological conditions via modulation of oxygen-, iron-, and 2-oxoglutarate-dependent dioxygenases.
abstract: Modern definitions of epigenetics incorporate models for transient but biologically important changes in gene expression that are unrelated to DNA code but responsive to environmental changes such as injury-induced stress. In this scheme, changes in oxygen levels (hypoxia) and/or metabolic co-factors (iron deficiency or diminished 2-oxoglutarate levels) are transduced into broad genetic programs that return the cell and the organism to a homeostatic set point. Over the past two decades, exciting studies have identified a superfamily of iron-, oxygen-, and 2-oxoglutarate-dependent dioxygenases that sit in the nucleus as modulators of transcription factor stability, co-activator function, histone demethylases, and DNA demethylases. These studies have provided a concrete molecular scheme for how changes in metabolism observed in a host of neurological conditions, including stroke, traumatic brain injury, and Alzheimer's disease, could be transduced into adaptive gene expression to protect the nervous system. We will discuss these enzymes in this short review, focusing primarily on the ten eleven translocation (TET) DNA demethylases, the jumonji (JmJc) histone demethylases, and the oxygen-sensing prolyl hydroxylase domain enzymes (HIF PHDs). This article is part of a Special Issue entitled SI: Neuroprotection.
authors.affiliation: Burke Medical Research Institute, White Plains, NY, USA; Feil Family Brain and Mind Research Institute, Department of Neurology, Weill Medical College of Cornell University, New York, NY, USA.
authors.forename: Saravanan S
authors.initials: SS
authors.lastname: Karuppagounder
authors.affiliation: Burke Medical Research Institute, White Plains, NY, USA; Feil Family Brain and Mind Research Institute, Department of Neurology, Weill Medical College of Cornell University, New York, NY, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Burke Medical Research Institute, White Plains, NY, USA; Feil Family Brain and Mind Research Institute, Department of Neurology, Weill Medical College of Cornell University, New York, NY, USA.
authors.forename: Diana S
authors.initials: DS
authors.lastname: Shao
authors.affiliation: Burke Medical Research Institute, White Plains, NY, USA; Feil Family Brain and Mind Research Institute, Department of Neurology, Weill Medical College of Cornell University, New York, NY, USA.
authors.forename: Marietta
authors.initials: M
authors.lastname: Zille
authors.affiliation: Burke Medical Research Institute, White Plains, NY, USA; Feil Family Brain and Mind Research Institute, Department of Neurology, Weill Medical College of Cornell University, New York, NY, USA.
authors.forename: Megan W
authors.initials: MW
authors.lastname: Bourassa
authors.affiliation: Burke Medical Research Institute, White Plains, NY, USA; Feil Family Brain and Mind Research Institute, Department of Neurology, Weill Medical College of Cornell University, New York, NY, USA.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Caulfield
authors.affiliation: Burke Medical Research Institute, White Plains, NY, USA; Feil Family Brain and Mind Research Institute, Department of Neurology, Weill Medical College of Cornell University, New York, NY, USA.
authors.forename: Ishraq
authors.initials: I
authors.lastname: Alim
authors.affiliation: Burke Medical Research Institute, White Plains, NY, USA; Feil Family Brain and Mind Research Institute, Department of Neurology, Weill Medical College of Cornell University, New York, NY, USA. Electronic address: rrr2001@med.cornell.edu.
authors.forename: Rajiv R
authors.initials: RR
authors.lastname: Ratan
mesh_terms: D000818:Animals; D049308:Dioxygenases / Q000378:metabolism*; D044127:Epigenesis, Genetic; D006801:Humans; D007501:Iron / Q000378:metabolism*; D009422:Nervous System Diseases / Q000235:genetics / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*
chemical_list: D007501:Iron; D049308:Dioxygenases; D010100:Oxygen
keywords: 2-Oxoglutarate-dependent dioxygenases; Brain; Epigenetics; Metabolism; Neuroprotection; Stroke