title: Paraoxonase-2 (PON2) in brain and its potential role in neuroprotection.
abstract: Paraoxonase 2 (PON2) is a member of a gene family which also includes the more studied PON1, as well as PON3. PON2 is unique among the three PONs, as it is expressed in brain tissue. PON2 is a lactonase and displays anti-oxidant and anti-inflammatory properties. PON2 levels are highest in dopaminergic regions (e.g. striatum), are higher in astrocytes than in neurons, and are higher in brain and peripheral tissues of female mice than male mice. At the sub-cellular level, PON2 localizes primarily in mitochondria, where it scavenges superoxides. Lack of PON2 (as in PON2(-/-) mice), or lower levels of PON2 (as in male mice compared to females) increases susceptibility to oxidative stress-induced toxicity. Estradiol increases PON2 expression in vitro and in vivo, and provides neuroprotection against oxidative stress. Such neuroprotection is not present in CNS cells from PON2(-/-) mice. Similar results are also found with the polyphenol quercetin. PON2, given its cellular localization and antioxidant and anti-inflammatory actions, may represent a relevant enzyme involved in neuroprotection, and may represent a novel target for neuroprotective strategies. Its differential expression in males and females may explain gender differences in the incidence of various diseases, including neurodevelopmental, neurological, and neurodegenerative diseases.
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA; Department of Neuroscience, University of Parma, Italy. Electronic address: lgcosta@u.washington.edu.
authors.forename: Lucio G
authors.initials: LG
authors.lastname: Costa
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Rian
authors.initials: R
authors.lastname: de Laat
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Khoi
authors.initials: K
authors.lastname: Dao
authors.affiliation: Department of Neuroscience, University of Parma, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pellacani
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA; Center on Human Development and Disability, University of Washington, Seattle, WA, USA; Division of Medical Genetics and Department of Genome Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Toby B
authors.initials: TB
authors.lastname: Cole
authors.affiliation: Division of Medical Genetics and Department of Genome Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Clement E
authors.initials: CE
authors.lastname: Furlong
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism* / Q000627:therapeutic use; D043303:Aryldialkylphosphatase / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D018696:Neuroprotective Agents; D043303:Aryldialkylphosphatase; C468411:PON2 protein, human
keywords: Gender differences; Neuroprotection; Oxidative stress; Paraoxonase 2