title: Emerging roles of Nrf2 and phase II antioxidant enzymes in neuroprotection.
abstract: Phase II metabolic enzymes are a battery of critical proteins that detoxify xenobiotics by increasing their hydrophilicity and enhancing their disposal. These enzymes have long been studied for their preventative and protective effects against mutagens and carcinogens and for their regulation via the Keap1 (Kelch-like ECH associated protein 1)/Nrf2 (Nuclear factor erythroid 2 related factor 2)/ARE (antioxidant response elements) pathway. Recently, a series of studies have reported the altered expression of phase II genes in postmortem tissue of patients with various neurological diseases. These observations hint at a role for phase II enzymes in the evolution of such conditions. Furthermore, promising findings reveal that overexpression of phase II genes, either by genetic or chemical approaches, confers neuroprotection in vitro and in vivo. Therefore, there is a need to summarize the current literature on phase II genes in the central nervous system (CNS). This should help guide future studies on phase II genes as therapeutic targets in neurological diseases. In this review, we first briefly introduce the concept of phase I, II and III enzymes, with a special focus on phase II enzymes. We then discuss their expression regulation, their inducers and executors. Following this background, we expand our discussion to the neuroprotective effects of phase II enzymes and the potential application of Nrf2 inducers to the treatment of neurological diseases.
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute of Brain Science, Fudan University, Shanghai, China.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Zhang
authors.forename: Chengrui
authors.initials: C
authors.lastname: An
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Gao
authors.forename: Rehana K
authors.initials: RK
authors.lastname: Leak
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002490:Central Nervous System / Q000201:enzymology; D006801:Humans; D050217:Metabolic Detoxication, Phase II / Q000502:physiology*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000201:enzymology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2