title: Linking lipid peroxidation and neuropsychiatric disorders: focus on 4-hydroxy-2-nonenal.
abstract: 4-hydroxy-2-nonenal (HNE) is considered to be a strong marker of oxidative stress; the interaction between HNE and cellular proteins leads to the formation of HNE-protein adducts able to alter cellular homeostasis and cause the development of a pathological state. By virtue of its high lipid concentration, oxygen utilization, and the presence of metal ions participating to redox reactions, the brain is highly susceptible to the formation of free radicals and HNE-related compounds. A variety of neuropsychiatric disorders have been associated with elevations of HNE concentration. For example, increased levels of HNE were found in the cortex of bipolar and schizophrenic patients, while HNE plasma concentrations resulted high in patients with major depression. On the same line, high brain concentrations of HNE were found associated with Huntington's inclusions. The incidence of high HNE levels is relevant also in the brain and cerebrospinal fluid of patients suffering from Parkinson's disease. Intriguingly, in this case the increase of HNE was associated with an accumulation of iron in the substantia nigra, a brain region highly affected by the pathology. In the present review we recapitulate the findings supporting the role of HNE in the pathogenesis of different neuropsychiatric disorders to highlight the pathogenic mechanisms ascribed to HNE accumulation. The aim of this review is to offer novel perspectives both for the understanding of etiopathogenetic mechanisms that remain still unclear and for the identification of new useful biological markers. We conclude suggesting that targeting HNE-driven cellular processes may represent a new more efficacious therapeutical intervention.
authors.affiliation: Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Piazzale A. Moro 5, 00185 Roma, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: Romano
authors.affiliation: Department of Medical and Surgical Sciences, University of Foggia, Via Luigi Pinto, c/o Ospedali Riuniti, 71122 Foggia, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Serviddio
authors.affiliation: Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Piazzale A. Moro 5, 00185 Roma, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Calcagnini
authors.affiliation: Department of Medical and Surgical Sciences, University of Foggia, Via Luigi Pinto, c/o Ospedali Riuniti, 71122 Foggia, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Villani
authors.affiliation: Department of Biological and Environmental Sciences and Technologies, University of Salento, Centro Ecotekne, sp Lecce-Monteroni 73100 Lecce, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Giudetti
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Via Luigi Pinto, c/o Ospedali Riuniti, 71122 Foggia, Italy. Electronic address: tommaso.cassano@unifg.it.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Cassano
authors.affiliation: Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Piazzale A. Moro 5, 00185 Roma, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Gaetani
mesh_terms: D000447:Aldehydes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001714:Bipolar Disorder / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy; D018696:Neuroprotective Agents / Q000627:therapeutic use; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D000447:Aldehydes; D018696:Neuroprotective Agents; D007501:Iron; C027576:4-hydroxy-2-nonenal
keywords: 4-hydroxy-2-nonenal; Huntington's disease; Parkinson's disease; bipolar disorders; depression; neuropsychiatric disorders; schizophrenia