The role of modulation of antioxidant enzyme systems in the treatment of neurodegenerative diseases

References

• Denzer I, Munch G, Friedland K. Modulation of mitochondrial dysfunction in neurodegenerative diseases via activation of nuclear factor erythroid-2-related factor 2 by food-derived compounds. Pharmacol Res 2016;103:80–94
   PubMed Web of Science ®Google Scholar
• Chen X, Guo C, Kong J. Oxidative stress in neurodegenerative diseases. Neural Regen Res 2012;7:376–85
   PubMed Web of Science ®Google Scholar
• Moreira PI, Cardoso SM, Santos MS, Oliveira CR. The key role of mitochondria in Alzheimer's disease. J Alzheimers Dis 2006;9:101–10
   PubMed Web of Science ®Google Scholar
• Nunomura A, Perry G, Aliev G, et al. Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 2001;60:759–67
   PubMed Web of Science ®Google Scholar
• Henchcliffe C, Beal MF. Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis. Nat Clin Pract Neurol 2008;4:600–9
   PubMedGoogle Scholar
• Bueler H. Impaired mitochondrial dynamics and function in the pathogenesis of Parkinson's disease. Exp Neurol 2009;218:235–46
   PubMed Web of Science ®Google Scholar
• Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 2006;443:787–95
   PubMed Web of Science ®Google Scholar
• Joshi G, Johnson JA. The Nrf2-ARE pathway: a valuable therapeutic target for the treatment of neurodegenerative diseases. Recent Pat CNS Drug Discov 2012;7:218–29
   PubMedGoogle Scholar
• Ma Q. Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol 2013;53:401–26
   PubMed Web of Science ®Google Scholar
• McMahon M, Itoh K, Yamamoto M, et al. The Cap‘n‘Collar basic leucine zipper transcription factor Nrf2 (NF-E2 p45-related factor 2) controls both constitutive and inducible expression of intestinal detoxification and glutathione biosynthetic enzymes. Cancer Res 2001;61:3299–307
   PubMed Web of Science ®Google Scholar
• Alam J, Stewart D, Touchard C, et al. Nrf2, a Cap‘n’Collar transcription factor, regulates induction of the heme oxygenase-1 gene. J Biol Chem 1999;274:26071–8
   PubMed Web of Science ®Google Scholar
• Barone MC, Sykiotis GP, Bohmann D. Genetic activation of Nrf2 signaling is sufficient to ameliorate neurodegenerative phenotypes in a Drosophila model of Parkinson's disease. Dis Model Mech 2011;4:701–7
   PubMed Web of Science ®Google Scholar
• Hubbs AF, Benkovic SA, Miller DB, et al. Vacuolar leukoencephalopathy with widespread astrogliosis in mice lacking transcription factor Nrf2. Am J Pathol 2007;170:2068–76
   PubMed Web of Science ®Google Scholar
• Rojo AI, Innamorato NG, Martin-Moreno AM, et al. Nrf2 regulates microglial dynamics and neuroinflammation in experimental Parkinson's disease. GLIA 2010;58:588–98
   PubMed Web of Science ®Google Scholar
• Kraft AD, Johnson DA, Johnson JA. Nuclear factor E2-related factor 2-dependent antioxidant response element activation by tert-butylhydroquinone and sulforaphane occurring preferentially in astrocytes conditions neurons against oxidative insult. J Neurosci 2004;24:1101–12
   PubMed Web of Science ®Google Scholar
• Jakel RJ, Townsend JA, Kraft AD, Johnson JA. Nrf2-mediated protection against 6-hydroxydopamine. Brain Res 2007;1144:192–201
   PubMed Web of Science ®Google Scholar
• Chen PC, Vargas MR, Pani AK, et al. Nrf2-mediated neuroprotection in the MPTP mouse model of Parkinson's disease: critical role for the astrocyte. Proc Natl Acad Sci USA 2009;106:2933–8
   PubMed Web of Science ®Google Scholar
• Calkins MJ, Jakel RJ, Johnson DA, et al. Protection from mitochondrial complex II inhibition in vitro and in vivo by Nrf2-mediated transcription. Proc Natl Acad Sci USA 2005;102:244–9
   PubMed Web of Science ®Google Scholar
• Facecchia K, Fochesato LA, Ray SD, et al. Oxidative toxicity in neurodegenerative diseases: role of mitochondrial dysfunction and therapeutic strategies. J Toxicol 2011;2011:683728
   PubMedGoogle Scholar
• Sehitoglu MH, Han H, Kalin P, et al. Pistachio (Pistacia vera L.) gum: a potent inhibitor of reactive oxygen species. J Enzyme Inhib Med Chem 2015;30:264–9
   PubMed Web of Science ®Google Scholar
• Topal F, Nar M, Gocer H, et al. Antioxidant activity of taxifolin: an activity–structure relationship. J Enzyme Inhib Med Chem 2016;31:674–83
   PubMed Web of Science ®Google Scholar
• Good PF, Hsu A, Werner P, et al. Protein nitration in Parkinson's disease. J Neuropathol Exp Neurol 1998;57:338–42
   PubMed Web of Science ®Google Scholar
• Hensley K, Maidt ML, Yu Z, et al. Electrochemical analysis of protein nitrotyrosine and dityrosine in the Alzheimer brain indicates region-specific accumulation. J Neurosci 1998;18:8126–32
   PubMed Web of Science ®Google Scholar
• Dexter DT, Carter CJ, Wells FR, et al. Basal lipid peroxidation in substantia nigra is increased in Parkinson's disease. J Neurochem 1989;52:381–9
   PubMed Web of Science ®Google Scholar
• Giasson BI, Duda JE, Murray IV, et al. Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science 2000;290:985–9
   PubMed Web of Science ®Google Scholar
• Horiguchi T, Uryu K, Giasson BI, et al. Nitration of tau protein is linked to neurodegeneration in tauopathies. Am J Pathol 2003;163:1021–31
   PubMed Web of Science ®Google Scholar
• Burdon RH, Rice-Evans C. Free radicals and the regulation of mammalian cell proliferation. Free Radic Res Commun 1989;6:345–58
   PubMedGoogle Scholar
• Burdon RH. Superoxide and hydrogen peroxide in relation to mammalian cell proliferation. Free Radic Biol Med 1995;18:775–94
   PubMed Web of Science ®Google Scholar
• Gulcin I. Antioxidant activity of food constituents: an overview. Arch Toxicol 2012;86:345–91
   PubMed Web of Science ®Google Scholar
• Zuo L, Zhou T, Pannell BK, et al. Biological and physiological role of reactive oxygen species-the good, the bad and the ugly. Acta Physiol (Oxf) 2015;214:329–48
   PubMed Web of Science ®Google Scholar
• Anderson G, Maes M. Neurodegeneration in Parkinson's disease: interactions of oxidative stress, tryptophan catabolites and depression with mitochondria and sirtuins. Mol Neurobiol 2014;49:771–83
   PubMed Web of Science ®Google Scholar
• Borquez DA, Urrutia PJ, Wilson C, et al. Dissecting the role of redox signaling in neuronal development. J Neurochem 2016;137:506–17
   PubMed Web of Science ®Google Scholar
• Wang K, Zhang T, Dong Q, et al. Redox homeostasis: the linchpin in stem cell self-renewal and differentiation. Cell Death Dis 2013;4:e537
   PubMed Web of Science ®Google Scholar
• MP M. How mitochondria produce reactive oxygen species. Biochemisrty 2009;417:1–13
   Google Scholar
• Cui H, Kong Y, Zhang H. Oxidative stress, mitochondrial dysfunction, and aging. J Signal Transduct 2012;2012:646354
   PubMedGoogle Scholar
• Muller WE, Eckert A, Kurz C, et al. Mitochondrial dysfunction: common final pathway in brain aging and Alzheimer's disease-therapeutic aspects. Mol Neurobiol 2010;41:159–71
   PubMed Web of Science ®Google Scholar
• Ryan BJ, Hoek S, Fon EA, Wade-Martins R. Mitochondrial dysfunction and mitophagy in Parkinson's: from familial to sporadic disease. Trends Biochem Sci 2015;40:200–10
   PubMed Web of Science ®Google Scholar
• Reddy TT, Kano A, Maruyama A, et al. Synthesis and characterization of semi-interpenetrating polymer networks based on polyurethane and N-isopropylacrylamide for wound dressing. J Biomed Mater Res Part B: Appl Biomater 2009;88:32–40
   PubMed Web of Science ®Google Scholar
• Grabacka MM, Gawin M, Pierzchalska M. Phytochemical modulators of mitochondria: the search for chemopreventive agents and supportive therapeutics. Pharmaceuticals (Basel) 2014;7:913–42
   PubMedGoogle Scholar
• Banerjee R, Starkov AA, Beal MF, Thomas B. Mitochondrial dysfunction in the limelight of Parkinson's disease pathogenesis. Biochim Biophys Acta 2009;1792:651–63
   PubMed Web of Science ®Google Scholar
• Gandhi S, Abramov AY. Mechanism of oxidative stress in neurodegeneration. Oxid Med Cell Longev 2012;2012:428010
   PubMed Web of Science ®Google Scholar
• Wang X, Su B, Siedlak SL, et al. Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins. Proc Natl Acad Sci USA 2008;105:19318–23
   PubMed Web of Science ®Google Scholar
• Wang X, Su B, Lee HG, et al. Impaired balance of mitochondrial fission and fusion in Alzheimer's disease. J Neurosci 2009;29:9090–103
   PubMed Web of Science ®Google Scholar
• Jiang Z, Wang W, Perry G, et al. Mitochondrial dynamic abnormalities in amyotrophic lateral sclerosis. Transl Neurodegener 2015;4:14
   PubMed Web of Science ®Google Scholar
• Santos D, Esteves AR, Silva DF, et al. The impact of mitochondrial fusion and fission modulation in sporadic Parkinson's disease. Mol Neurobiol 2015;52:573–86
   PubMed Web of Science ®Google Scholar
• Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 2007;87:245–313
   PubMed Web of Science ®Google Scholar
• Edmondson DE. Hydrogen peroxide produced by mitochondrial monoamine oxidase catalysis: biological implications. Curr Pharm Des 2014;20:155–60
   PubMed Web of Science ®Google Scholar
• Alderton WK, Cooper CE, Knowles RG. Nitric oxide synthases: structure, function and inhibition. Biochem J 2001;357:593–615
   PubMed Web of Science ®Google Scholar
• Shahraki A, Stone TW. Blockade of presynaptic adenosine A1 receptor responses by nitric oxide and superoxide in rat hippocampus. Eur J Neurosci 2004;20:719–28
   PubMed Web of Science ®Google Scholar
• Ukeda DK H, Maeda S, Sawamura M. Spectrophotometric assay for superoxide dismutase based on the reduction of highly water-soluble tetrazolium salts by xanthine–xanthine oxidase. Biosci Biotechnol Biochem 1999;63:485–8
   PubMed Web of Science ®Google Scholar
• Tammariello SP, Quinn MT, Estus S. NADPH oxidase contributes directly to oxidative stress and apoptosis in nerve growth factor-deprived sympathetic neurons. J Neurosci 2000;20:RC53
   PubMed Web of Science ®Google Scholar
• Hernandes MS, Britto LR. NADPH oxidase and neurodegeneration. Curr Neuropharmacol 2012;10:321–7
   PubMed Web of Science ®Google Scholar
• Sorce S, Krause KH. NOX enzymes in the central nervous system: from signaling to disease. Antioxid Redox Signal 2009;11:2481–504
   PubMed Web of Science ®Google Scholar
• Emilsson L, Saetre P, Balciuniene J, et al. Increased monoamine oxidase messenger RNA expression levels in frontal cortex of Alzheimer's disease patients. Neurosci Lett 2002;326:56–60
   PubMed Web of Science ®Google Scholar
• Mallajosyula JK, Kaur D, Chinta SJ, et al. MAO-B elevation in mouse brain astrocytes results in Parkinson's pathology. PLoS One 2008;3:e1616
   PubMed Web of Science ®Google Scholar
• Nguyen T, Nioi P, Pickett CB. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem 2009;284:13291–5
   PubMed Web of Science ®Google Scholar
• Itoh K, Chiba T, Takahashi S, et al. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun 1997;236:313–22
   PubMed Web of Science ®Google Scholar
• Itoh K, Wakabayashi N, Katoh Y, et al. Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev 1999;13:76–86
   PubMed Web of Science ®Google Scholar
• Zipper LM, Mulcahy RT. The Keap1 BTB/POZ dimerization function is required to sequester Nrf2 in cytoplasm. J Biol Chem 2002;277:36544–52
   PubMed Web of Science ®Google Scholar
• Wakabayashi N, Itoh K, Wakabayashi J, et al. Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Nat Genet 2003;35:238–45
   PubMed Web of Science ®Google Scholar
• McMahon M, Itoh K, Yamamoto M, Hayes JD. Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression. J Biol Chem 2003;278:21592–600
   PubMed Web of Science ®Google Scholar
• Itoh K, Wakabayashi N, Katoh Y, et al. Keap1 regulates both cytoplasmic-nuclear shuttling and degradation of Nrf2 in response to electrophiles. Genes Cells 2003;8:379–91
   PubMed Web of Science ®Google Scholar
• Nguyen T, Sherratt PJ, Huang HC, et al. Increased protein stability as a mechanism that enhances Nrf2-mediated transcriptional activation of the antioxidant response element. Degradation of Nrf2 by the 26 S proteasome. J Biol Chem 2003;278:4536–41
   PubMed Web of Science ®Google Scholar
• Zhang DD, Lo SC, Cross JV, et al. Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. Mol Cell Biol 2004;24:10941–53
   PubMed Web of Science ®Google Scholar
• Eggler AL, Liu G, Pezzuto JM, et al. Modifying specific cysteines of the electrophile-sensing human Keap1 protein is insufficient to disrupt binding to the Nrf2 domain Neh2. Proc Natl Acad Sci USA 2005;102:10070–5
   PubMed Web of Science ®Google Scholar
• Zhang DD. Mechanistic studies of the Nrf2-Keap1 signaling pathway. Drug Metab Rev 2006;38:769–89
   PubMed Web of Science ®Google Scholar
• Ishii T, Itoh K, Takahashi S, et al. Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages. J Biol Chem 2000;275:16023–9
   PubMed Web of Science ®Google Scholar
• Wild AC, Moinova HR, Mulcahy RT. Regulation of gamma-glutamylcysteine synthetase subunit gene expression by the transcription factor Nrf2. J Biol Chem 1999;274:33627–36
   PubMed Web of Science ®Google Scholar
• Sekhar KR, Yan XX, Freeman ML. Nrf2 degradation by the ubiquitin proteasome pathway is inhibited by KIAA0132, the human homolog to INrf2. Oncogene 2002;21:6829–34
   PubMed Web of Science ®Google Scholar
• Stewart D, Killeen E, Naquin R, et al. Degradation of transcription factor Nrf2 via the ubiquitin-proteasome pathway and stabilization by cadmium. J Biol Chem 2003;278:2396–402
   PubMed Web of Science ®Google Scholar
• Zhang DD, Hannink M. Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. Mol Cell Biol 2003;23:8137–51
   PubMed Web of Science ®Google Scholar
• Kobayashi A, Kang MI, Okawa H, et al. Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Mol Cell Biol 2004;24:7130–9
   PubMed Web of Science ®Google Scholar
• Cullinan SB, Gordan JD, Jin J, et al. The Keap1–BTB protein is an adaptor that bridges Nrf2 to a Cul3-based E3 ligase: oxidative stress sensing by a Cul3–Keap1 ligase. Mol Cell Biol 2004;24:8477–86
   PubMed Web of Science ®Google Scholar
• Furukawa M, Xiong Y. BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the Cullin 3-Roc1 ligase. Mol Cell Biol 2005;25:162–71
   PubMed Web of Science ®Google Scholar
• Dinkova-Kostova AT, Holtzclaw WD, Cole RN, et al. Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proc Natl Acad Sci USA 2002;99:11908–13
   PubMed Web of Science ®Google Scholar
• Yamamoto T, Suzuki T, Kobayashi A, et al. Physiological significance of reactive cysteine residues of Keap1 in determining Nrf2 activity. Mol Cell Biol 2008;28:2758–70
   PubMed Web of Science ®Google Scholar
• Dinkova-Kostova AT, Holtzclaw WD, Wakabayashi N. Keap1, the sensor for electrophiles and oxidants that regulates the phase 2 response, is a zinc metalloprotein. Biochemistry 2005;44:6889–99
   PubMed Web of Science ®Google Scholar
• Luo Y, Eggler AL, Liu D, et al. Sites of alkylation of human Keap1 by natural chemoprevention agents. J Am Soc Mass Spectrom 2007;18:2226–32
   PubMed Web of Science ®Google Scholar
• Wang XJ, Sun Z, Chen W, et al. Activation of Nrf2 by arsenite and monomethylarsonous acid is independent of Keap1–C151: enhanced Keap1–Cul3 interaction. Toxicol Appl Pharmacol 2008;230:383–9
   PubMed Web of Science ®Google Scholar
• Kobayashi M, Li L, Iwamoto N, et al. The antioxidant defense system Keap1–Nrf2 comprises a multiple sensing mechanism for responding to a wide range of chemical compounds. Mol Cell Biol 2009;29:493–502
   PubMed Web of Science ®Google Scholar
• Sekhar KR, Rachakonda G, Freeman ML. Cysteine-based regulation of the CUL3 adaptor protein Keap1. Toxicol Appl Pharmacol 2010;244:21–6
   PubMed Web of Science ®Google Scholar
• Li X, Zhang D, Hannink M, Beamer LJ. Crystal structure of the Kelch domain of human Keap1. J Biol Chem 2004;279:54750–8
   PubMed Web of Science ®Google Scholar
• Katoh Y, Iida K, Kang MI, et al. Evolutionary conserved N-terminal domain of Nrf2 is essential for the Keap1-mediated degradation of the protein by proteasome. Arch Biochem Biophys 2005;433:342–50
   PubMed Web of Science ®Google Scholar
• Lo SC, Li X, Henzl MT, et al. Structure of the Keap1: Nrf2 interface provides mechanistic insight into Nrf2 signaling. EMBO J 2006;25:3605–17
   PubMed Web of Science ®Google Scholar
• Padmanabhan B, Tong KI, Ohta T, et al. Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer. Mol Cell 2006;21:689–700
   PubMed Web of Science ®Google Scholar
• McMahon M, Thomas N, Itoh K, et al. Dimerization of substrate adaptors can facilitate cullin-mediated ubiquitylation of proteins by a “el for the Nrf2-Keap1 complex” mechanism: a two-site interaction model for the Nrf2-Keap1. J Biol Chem 2006;281:24756–68
   PubMed Web of Science ®Google Scholar
• Tong KI, Kobayashi A, Katsuoka F, Yamamoto M. Two-site substrate recognition model for the Keap1–Nrf2 system: a hinge and latch mechanism. Biol Chem 2006;387:1311–20
   PubMed Web of Science ®Google Scholar
• Ogura T, Tong KI, Mio K, et al. Keap1 is a forked-stem dimer structure with two large spheres enclosing the intervening, double glycine repeat, and C-terminal domains. Proc Natl Acad Sci USA 2010;107:2842–7
   PubMed Web of Science ®Google Scholar
• Cleasby A, Yon J, Day PJ, et al. Structure of the BTB domain of Keap1 and its interaction with the triterpenoid antagonist CDDO. PLoS One 2014;9:e98896
   PubMed Web of Science ®Google Scholar
• Canning P, Sorrell FJ, Bullock AN. Structural basis of Keap1 interactions with Nrf2. Free Radic Biol Med 2015;88:101–7
   PubMed Web of Science ®Google Scholar
• Yu R, Lei W, Mandlekar S, et al. Role of a mitogen-activated protein kinase pathway in the induction of phase II detoxifying enzymes by chemicals. J Biol Chem 1999;274:27545–52
   PubMed Web of Science ®Google Scholar
• Lee JM, Hanson JM, Chu WA, Johnson JA. Phosphatidylinositol 3-kinase, not extracellular signal-regulated kinase, regulates activation of the antioxidant-responsive element in IMR-32 human neuroblastoma cells. J Biol Chem 2001;276:20011–16
   PubMed Web of Science ®Google Scholar
• Huang HC, Nguyen T, Pickett CB. Regulation of the antioxidant response element by protein kinase C-mediated phosphorylation of NF-E2-related factor 2. Proc Natl Acad Sci USA 2000;97:12475–80
   PubMed Web of Science ®Google Scholar
• Huang HC, Nguyen T, Pickett CB. Phosphorylation of Nrf2 at Ser-40 by protein kinase C regulates antioxidant response element-mediated transcription. J Biol Chem 2002;277:42769–74
   PubMed Web of Science ®Google Scholar
• Numazawa S, Ishikawa M, Yoshida A, et al. Atypical protein kinase C mediates activation of NF-E2-related factor 2 in response to oxidative stress. Am J Physiol Cell Physiol 2003;285:C334–42
   PubMed Web of Science ®Google Scholar
• Bloom DA, Jaiswal AK. Phosphorylation of Nrf2 at Ser40 by protein kinase C in response to antioxidants leads to the release of Nrf2 from INrf2, but is not required for Nrf2 stabilization/accumulation in the nucleus and transcriptional activation of antioxidant response element-mediated NAD(P)H: quinone oxidoreductase-1 gene expression. J Biol Chem 2003;278:44675–82
   PubMed Web of Science ®Google Scholar
• Salazar M, Rojo AI, Velasco D, et al. Glycogen synthase kinase-3beta inhibits the xenobiotic and antioxidant cell response by direct phosphorylation and nuclear exclusion of the transcription factor Nrf2. J Biol Chem 2006;281:14841–51
   PubMed Web of Science ®Google Scholar
• Li L, Dong H, Song E, et al. Nrf2/ARE pathway activation, HO-1 and NQO1 induction by polychlorinated biphenyl quinone is associated with reactive oxygen species and PI3K/AKT signaling. Chem Biol Interact 2014;209:56–67
   PubMed Web of Science ®Google Scholar
• Espada S, Rojo AI, Salinas M, Cuadrado A. The muscarinic M1 receptor activates Nrf2 through a signaling cascade that involves protein kinase C and inhibition of GSK-3beta: connecting neurotransmission with neuroprotection. J Neurochem 2009;110:1107–19
   PubMed Web of Science ®Google Scholar
• Tan Y, Ichikawa T, Li J, et al. Diabetic downregulation of Nrf2 activity via ERK contributes to oxidative stress-induced insulin resistance in cardiac cells in vitro and in vivo. Diabetes 2011;60:625–33
   PubMed Web of Science ®Google Scholar
• Jain AK, Jaiswal AK. GSK-3beta acts upstream of Fyn kinase in regulation of nuclear export and degradation of NF-E2 related factor 2. J Biol Chem 2007;282:16502–10
   PubMed Web of Science ®Google Scholar
• Niture SK, Jain AK, Shelton PM, Jaiswal AK. Src subfamily kinases regulate nuclear export and degradation of transcription factor Nrf2 to switch off Nrf2-mediated antioxidant activation of cytoprotective gene expression. J Biol Chem 2011;286:28821–32
   PubMed Web of Science ®Google Scholar
• Rojo AI, Sagarra MR, Cuadrado A. GSK-3beta down-regulates the transcription factor Nrf2 after oxidant damage: relevance to exposure of neuronal cells to oxidative stress. J Neurochem 2008;105:192–202
   PubMed Web of Science ®Google Scholar
• Rada P, Rojo AI, Chowdhry S, et al. SCF/{beta}-TrCP promotes glycogen synthase kinase 3-dependent degradation of the Nrf2 transcription factor in a Keap1-independent manner. Mol Cell Biol 2011;31:1121–33
   PubMed Web of Science ®Google Scholar
• Rada P, Rojo AI, Evrard-Todeschi N, et al. Structural and functional characterization of Nrf2 degradation by the glycogen synthase kinase 3/beta-TrCP axis. Mol Cell Biol 2012;32:3486
   PubMed Web of Science ®Google Scholar
• Rojo AI, Medina-Campos ON, Rada P, et al. Signaling pathways activated by the phytochemical nordihydroguaiaretic acid contribute to a Keap1-independent regulation of Nrf2 stability: role of glycogen synthase kinase-3. Free Radic Biol Med 2012;52:473–87
   PubMed Web of Science ®Google Scholar
• Chowdhry S, Zhang Y, McMahon M, et al. Nrf2 is controlled by two distinct beta-TrCP recognition motifs in its Neh6 domain, one of which can be modulated by GSK-3 activity. Oncogene 2013;32:3765–81
   PubMed Web of Science ®Google Scholar
• Lewis KN, Wason E, Edrey YH, et al. Regulation of Nrf2 signaling and longevity in naturally long-lived rodents. Proc Natl Acad Sci USA 2015;112:3722–7
   PubMed Web of Science ®Google Scholar
• Lee WH, Loo CY, Bebawy M, et al. Curcumin and its derivatives: their application in neuropharmacology and neuroscience in the 21st century. Curr Neuropharmacol 2013;11:338–78
   PubMed Web of Science ®Google Scholar
• Ak T, Gulcin I. Antioxidant and radical scavenging properties of curcumin. Chem Biol Interact 2008;174:27–37
   PubMed Web of Science ®Google Scholar
• Cui Q, Li X, Zhu H. Curcumin ameliorates dopaminergic neuronal oxidative damage via activation of the Akt/Nrf2 pathway. Mol Med Rep 2016;13:1381–8
   PubMed Web of Science ®Google Scholar
• Narayanan SV, Dave KR, Saul I, Perez-Pinzon MA. Resveratrol preconditioning protects against cerebral ischemic injury via nuclear erythroid 2-related factor 2. Stroke 2015;46:1626–32
   PubMed Web of Science ®Google Scholar
• Braidy N, Jugder BE, Poljak A, et al. Resveratrol as a potential therapeutic candidate for the treatment and management of Alzheimer's disease. Curr Top Med Chem 2016;16:1951–60
   PubMed Web of Science ®Google Scholar
• Ringman JM, Frautschy SA, Cole GM, et al. A potential role of the curry spice curcumin in Alzheimer's disease. Curr Alzheimer Res 2005;2:131–6
   PubMedGoogle Scholar
• Dinkova-Kostova AT, Talalay P. Relation of structure of curcumin analogs to their potencies as inducers of Phase 2 detoxification enzymes. Carcinogenesis 1999;20:911–14
   PubMed Web of Science ®Google Scholar
• Baum L, Lam CW, Cheung SK, et al. Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J Clin Psychopharmacol 2008;28:110–13
   PubMed Web of Science ®Google Scholar
• Ringman JM, Frautschy SA, Teng E, et al. Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study. Alzheimers Res Ther 2012;4:43
   PubMed Web of Science ®Google Scholar
• Turner RS, Thomas RG, Craft S, et al. A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology 2015;85:1383–91
   PubMed Web of Science ®Google Scholar
• Li R, Zheng N, Liang T, et al. Puerarin attenuates neuronal degeneration and blocks oxidative stress to elicit a neuroprotective effect on substantia nigra injury in 6-OHDA-lesioned rats. Brain Res 2013;1517:28–35
   PubMed Web of Science ®Google Scholar
• Wang XL, Xing GH, Hong B, et al. Gastrodin prevents motor deficits and oxidative stress in the MPTP mouse model of Parkinson's disease: involvement of ERK1/2-Nrf2 signaling pathway. Life Sci 2014;114:77–85
   PubMed Web of Science ®Google Scholar
• Kim S, Lee HG, Park SA, et al. Keap1 cysteine 288 as a potential target for diallyl trisulfide-induced Nrf2 activation. PLoS One 2014;9:e85984
   PubMed Web of Science ®Google Scholar
• Kim HV, Kim HY, Ehrlich HY, et al. Amelioration of Alzheimer's disease by neuroprotective effect of sulforaphane in animal model. Amyloid 2013;20:7–12
   PubMed Web of Science ®Google Scholar
• Morroni F, Tarozzi A, Sita G, et al. Neuroprotective effect of sulforaphane in 6-hydroxydopamine-lesioned mouse model of Parkinson's disease. Neurotoxicology 2013;36:63–71
   PubMed Web of Science ®Google Scholar
• Li XH, Li CY, Xiang ZG, et al. Allicin can reduce neuronal death and ameliorate the spatial memory impairment in Alzheimer's disease models. Neurosciences (Riyadh) 2010;15:237–43
   PubMed Web of Science ®Google Scholar
• Li XH, Li CY, Lu JM, et al. Allicin ameliorates cognitive deficits ageing-induced learning and memory deficits through enhancing of Nrf2 antioxidant signaling pathways. Neurosci Lett 2012;514:46–50
   PubMed Web of Science ®Google Scholar
• Zhu YF, Li XH, Yuan ZP, et al. Allicin improves endoplasmic reticulum stress-related cognitive deficits via PERK/Nrf2 antioxidative signaling pathway. Eur J Pharmacol 2015;762:239–46
   PubMed Web of Science ®Google Scholar
• Trinh K, Andrews L, Krause J, et al. Decaffeinated coffee and nicotine-free tobacco provide neuroprotection in Drosophila models of Parkinson's disease through an NRF2-dependent mechanism. J Neurosci 2010;30:5525–32
   PubMed Web of Science ®Google Scholar
• Liby KT, Sporn MB. Synthetic oleanane triterpenoids: multifunctional drugs with a broad range of applications for prevention and treatment of chronic disease. Pharmacol Rev 2012;64:972–1003
   PubMed Web of Science ®Google Scholar
• Honda T, Rounds BV, Gribble GW, et al. Design and synthesis of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, a novel and highly active inhibitor of nitric oxide production in mouse macrophages. Bioorg Med Chem Lett 1998;8:2711–14
   PubMed Web of Science ®Google Scholar
• Suh N, Wang Y, Honda T, et al. A novel synthetic oleanane triterpenoid, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, with potent differentiating, antiproliferative, and anti-inflammatory activity. Cancer Res 1999;59:336–41
   PubMed Web of Science ®Google Scholar
• Sporn MB, Liby KT, Yore MM, et al. New synthetic triterpenoids: potent agents for prevention and treatment of tissue injury caused by inflammatory and oxidative stress. J Nat Prod 2011;74:537–45
   PubMed Web of Science ®Google Scholar
• Honda T, Rounds BV, Bore L, et al. Synthetic oleanane and ursane triterpenoids with modified rings A and C: a series of highly active inhibitors of nitric oxide production in mouse macrophages. J Med Chem 2000;43:4233–46
   PubMed Web of Science ®Google Scholar
• Liby K, Hock T, Yore MM, et al. The synthetic triterpenoids, CDDO and CDDO-imidazolide, are potent inducers of heme oxygenase-1 and Nrf2/ARE signaling. Cancer Res 2005;65:4789–98
   PubMed Web of Science ®Google Scholar
• Ahmad R, Raina D, Meyer C, et al. Triterpenoid CDDO-Me blocks the NF-kappaB pathway by direct inhibition of IKKbeta on Cys-179. J Biol Chem 2006;281:35764–9
   PubMed Web of Science ®Google Scholar
• Yore MM, Liby KT, Honda T, et al. The synthetic triterpenoid 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole blocks nuclear factor-kappaB activation through direct inhibition of IkappaB kinase beta. Mol Cancer Ther 2006;5:3232
   PubMed Web of Science ®Google Scholar
• Thimmulappa RK, Scollick C, Traore K, et al. Nrf2-dependent protection from LPS induced inflammatory response and mortality by CDDO-Imidazolide. Biochem Biophys Res Commun 2006;351:883–9
   PubMed Web of Science ®Google Scholar
• Dumont M, Wille E, Calingasan NY, et al. Triterpenoid CDDO-methylamide improves memory and decreases amyloid plaques in a transgenic mouse model of Alzheimer's disease. J Neurochem 2009;109:502–12
   PubMed Web of Science ®Google Scholar
• Yang L, Calingasan NY, Thomas B, et al. Neuroprotective effects of the triterpenoid, CDDO methyl amide, a potent inducer of Nrf2-mediated transcription. PLoS One 2009;4:e5757
   PubMed Web of Science ®Google Scholar
• Kaidery NA, Banerjee R, Yang L, et al. Targeting Nrf2-mediated gene transcription by extremely potent synthetic triterpenoids attenuate dopaminergic neurotoxicity in the MPTP mouse model of Parkinson's disease. Antioxid Redox Signal 2013;18:139–57
   PubMed Web of Science ®Google Scholar
• Neymotin A, Calingasan NY, Wille E, et al. Neuroprotective effect of Nrf2/ARE activators, CDDO ethylamide and CDDO trifluoroethylamide, in a mouse model of amyotrophic lateral sclerosis. Free Radic Biol Med 2011;51:88–96
   PubMed Web of Science ®Google Scholar
• Stack C, Ho D, Wille E, et al. Triterpenoids CDDO-ethyl amide and CDDO-trifluoroethyl amide improve the behavioral phenotype and brain pathology in a transgenic mouse model of Huntington's disease. Free Radic Biol Med 2010;49:147–58
   PubMed Web of Science ®Google Scholar
• Takagi T, Kitashoji A, Iwawaki T, et al. Temporal activation of Nrf2 in the penumbra and Nrf2 activator-mediated neuroprotection in ischemia-reperfusion injury. Free Radic Biol Med 2014;72:124–33
   PubMed Web of Science ®Google Scholar
• de Zeeuw D, Akizawa T, Audhya P, et al. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. N Engl J Med 2013;369:2492–503
   PubMed Web of Science ®Google Scholar
• Zhang DD. Bardoxolone brings Nrf2-based therapies to light. Antioxid Redox Signal 2013;19:517–18
   PubMed Web of Science ®Google Scholar
• Gold R, Kappos L, Arnold DL, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med 2012;367:1098–107
   PubMed Web of Science ®Google Scholar
• Fox RJ, Miller DH, Phillips JT, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med 2012;367:1087–97
   PubMed Web of Science ®Google Scholar
• Scannevin RH, Chollate S, Jung MY, et al. Fumarates promote cytoprotection of central nervous system cells against oxidative stress via the nuclear factor (erythroid-derived 2)-like 2 pathway. J Pharmacol Exp Ther 2012;341:274–84
   PubMed Web of Science ®Google Scholar
• Ellrichmann G, Petrasch-Parwez E, Lee DH, et al. Efficacy of fumaric acid esters in the R6/2 and YAC128 models of Huntington's disease. PLoS One 2011;6:e16172
   PubMed Web of Science ®Google Scholar
• Wang Q, Chuikov S, Taitano S, et al. Dimethyl fumarate protects neural stem/progenitor cells and neurons from oxidative damage through Nrf2-ERK1/2 MAPK pathway. Int J Mol Sci 2015;16:13885–907
   PubMed Web of Science ®Google Scholar
• Wu JZ, Cheng CC, Shen LL, et al. Synthetic chalcones with potent antioxidant ability on H(2)O(2)-induced apoptosis in PC12 cells. Int J Mol Sci 2014;15:18525–39
   PubMed Web of Science ®Google Scholar
• Kaufmann KB, Al-Rifai N, Ulbrich F, et al. The cytoprotective effects of E-alpha-(4-methoxyphenyl)-2′,3,4,4′-tetramethoxychalcone (E-alpha-p-OMe-C6H4-TMC) – a novel and non-cytotoxic HO-1 inducer. PLoS One 2015;10:e0142932
   Google Scholar
• Otterbein LE, Bach FH, Alam J, et al. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 2000;6:422–8
   PubMed Web of Science ®Google Scholar
• Gullotta F, di Masi A, Ascenzi P. Carbon monoxide: an unusual drug. IUBMB Life 2012;64:378–86
   PubMed Web of Science ®Google Scholar
• Wilson JL, Fayad Kobeissi S, Oudir S, et al. Design and synthesis of new hybrid molecules that activate the transcription factor Nrf2 and simultaneously release carbon monoxide. Chemistry 2014;20:14698–704
   PubMed Web of Science ®Google Scholar
• Nikam A, Ollivier A, Rivard M, et al. Diverse Nrf2 activators coordinated to cobalt carbonyls induce heme oxygenase-1 and release carbon monoxide in vitro and in vivo. J Med Chem 2016;59:756–62
   PubMed Web of Science ®Google Scholar
• Go ML, Wu X, Liu XL. Chalcones: an update on cytotoxic and chemoprotective properties. Curr Med Chem 2005;12:481–99
   PubMed Web of Science ®Google Scholar
• Nowakowska Z. A review of anti-infective and anti-inflammatory chalcones. Eur J Med Chem 2007;42:125–37
   PubMed Web of Science ®Google Scholar
• Sawle P, Moulton BE, Jarzykowska M, et al. Structure–activity relationships of methoxychalcones as inducers of heme oxygenase-1. Chem Res Toxicol 2008;21:1484–94
   PubMed Web of Science ®Google Scholar
• Jin F, Jin XY, Jin YL, et al. Structural requirements of 2′,4′,6′-tris(methoxymethoxy) chalcone derivatives for anti-inflammatory activity: the importance of a 2′-hydroxy moiety. Arch Pharm Res 2007;30:1359–67
   PubMed Web of Science ®Google Scholar
• Kumar V, Kumar S, Hassan M, et al. Novel chalcone derivatives as potent Nrf2 activators in mice and human lung epithelial cells. J Med Chem 2011;54:4147–59
   PubMed Web of Science ®Google Scholar
• Lounsbury N, Mateo G, Jones B, et al. Heterocyclic chalcone activators of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) with improved in vivo efficacy. Bioorg Med Chem 2015;23:5352–9
   PubMed Web of Science ®Google Scholar
• Wells G. Peptide and small molecule inhibitors of the Keap1–Nrf2 protein–protein interaction. Biochem Soc Trans 2015;43:674–9
   PubMed Web of Science ®Google Scholar
• Abed DA, Goldstein M, Albanyan H, et al. Discovery of direct inhibitors of Keap1–Nrf2 protein–protein interaction as potential therapeutic and preventive agents. Acta Pharm Sin B 2015;5:285–99
   PubMed Web of Science ®Google Scholar
• Hu L, Magesh S, Chen L, et al. Discovery of a small-molecule inhibitor and cellular probe of Keap1–Nrf2 protein–protein interaction. Bioorg Med Chem Lett 2013;23:3039–43
   PubMed Web of Science ®Google Scholar
• Marcotte D, Zeng W, Hus JC, et al. Small molecules inhibit the interaction of Nrf2 and the Keap1 Kelch domain through a non-covalent mechanism. Bioorg Med Chem 2013;21:4011–19
   PubMed Web of Science ®Google Scholar
• Jiang ZY, Lu MC, Xu LL, et al. Discovery of potent Keap1–Nrf2 protein–protein interaction inhibitor based on molecular binding determinants analysis. J Med Chem 2014;57:2736–45
   PubMed Web of Science ®Google Scholar
• Davies TG, Wixted WE, Coyle JE, et al. Monoacidic inhibitors of the Kelch-like ECH-associated protein 1: nuclear factor erythroid 2-related factor 2 (KEAP1:NRF2) protein–protein interaction with high cell potency identified by fragment-based discovery. J Med Chem 2016;59:3991–4006
   PubMed Web of Science ®Google Scholar
• Fox RJ, Kita M, Cohan SL, et al. BG-12 (dimethyl fumarate): a review of mechanism of action, efficacy, and safety. Curr Med Res Opin 2014;30:251–62
   PubMed Web of Science ®Google Scholar