title: Hormesis, cellular stress response and neuroinflammation in schizophrenia: Early onset versus late onset state.
abstract: Abnormal redox homeostasis and oxidative stress have been proposed to play a role in the etiology of several neuropsychiatric spectrum disorders. Emerging interest has recently focused on markers of oxidative stress and neuroinflammation in schizophrenic spectrum disorders, at least in particular subgroups of patients. Altered expression of genes related to oxidative stress, oxidative damage to DNA, protein and lipids, as well as reduced glutathione levels in central and peripheral tissues could act synergistically, and contribute to the course of the disease.  Herein, we discuss cellular mechanisms that may be operative in neuroinflammation and contributory to schizophrenia. We address modulation of endogenous cellular defense mechanisms as a potentially innovative approach to therapeutics for schizophrenia, and other neuropsychiatric conditions that are associated with neuroinflammation. Specifically, we discuss the emerging role of heme oxygenase as prominent member of neuroprotective network in redox stress responsive mechanisms, as well as the importance of glutathione relevant in schizophrenia pathophysiology. Finally we introduce the hormetic dose response concept as relevant and important to neuroprotection, and review hormetic mechanisms as possible approaches to manipulation of neuroinflammatory targets that may be viable for treating schizophrenia spectrum disorders. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Calabrese
authors.affiliation: Departments of Neurology and Biochemistry; and Neuroethics Studies Program, Pellegrino Center for Clinical Bioethics, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: James
authors.initials: J
authors.lastname: Giordano
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Rosalia
authors.initials: R
authors.lastname: Crupi
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.affiliation: Department of Clinical and Experimental Medicine, School of Medicine, University of Catania, Catania, Italy.
authors.forename: Martino
authors.initials: M
authors.lastname: Ruggieri
authors.affiliation: Department of Clinical and Experimental Medicine, School of Medicine, University of Catania, Catania, Italy.
authors.forename: Rio
authors.initials: R
authors.lastname: Bianchini
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Ontario
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.affiliation: Environmental Health Sciences Division, School of Public Health, University of Massachusetts, Amherst, Massachusetts, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Calabrese
mesh_terms: D000818:Animals; D004660:Encephalitis / Q000188:drug therapy / Q000209:etiology*; D018869:Heat-Shock Response; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D059165:Hormesis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D028361:Mitochondrial Diseases / Q000209:etiology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D012559:Schizophrenia / Q000150:complications*
chemical_list: D018696:Neuroprotective Agents; D006419:Heme Oxygenase (Decyclizing)
keywords: glutathione; heme oxygenase; hormesis; pathophysiology; schizophrenia; vitagenes