title: SOD1 and DJ-1 converge at Nrf2 pathway: a clue for antioxidant therapeutic potential in neurodegeneration.
abstract: Neurodegenerative diseases share diverse pathological features and among these oxidative stress (OS) plays a leading role. Impaired activity and reduced expression of antioxidant proteins have been reported as common events in several aging-associated disorders. In this review paper, we first provide an overview of the involvement of reactive oxygen species- (ROS-) induced oxidative damage in Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). Subsequently, we focus on DJ-1 and SOD1 proteins, which are involved in PD and ALS and also exert a prominent role in the interaction between redox homeostasis and neurodegeneration. Interestingly, recent studies demonstrated that DJ-1 and SOD1 are both tightly connected with Nrf2 protein, a transcriptional factor and master regulator of the expression of many antioxidant/detoxification genes. Nrf2 is emerging as a key neuroprotective protein in neurodegenerative diseases, since it helps neuronal cells to cope with toxic insults and OS. We herein summarize the recent literature providing a detailed picture of the promising therapeutic efficacy of Nrf2 natural and synthetic inducers as disease-modifying molecules for the treatment of neurodegenerative diseases.
authors: Laboratory of Experimental Neurobiology, National Neurological Institute C. Mondino, IRCCS, Pavia, Italy. pame.milani@gmail.com
authors: Pamela
authors: P
authors: Milani
authors: Giulia
authors: G
authors: Ambrosi
authors: Omar
authors: O
authors: Gammoh
authors: Fabio
authors: F
authors: Blandini
authors: Cristina
authors: C
authors: Cereda
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D000071617:Protein Deglycase DJ-1; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: D000975:Antioxidants; D047908:Intracellular Signaling Peptides and Proteins; D051267:NF-E2-Related Factor 2; D015513:Oncogene Proteins; D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1
references: Antioxid Redox Signal. 2011 Jul 1;15(1):111-22
references: 20812780
references: Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14807-12
references: 17766438
references: J Mol Neurosci. 2013 Feb;49(2):262-9
references: 22706709
references: J Neurochem. 2008 Feb;104(4):1116-31
references: 17995931
references: Cell Biol Int. 2008 Jan;32(1):22-30
references: 17936647
references: Clin Chim Acta. 2006 Feb;364(1-2):217-21
references: 16109392
references: J Biol Chem. 2003 Aug 15;278(33):31380-4
references: 12796482
references: Mitochondrion. 2005 Apr;5(2):77-87
references: 16050975
references: J Biol Chem. 1969 Nov 25;244(22):6049-55
references: 5389100
references: Drugs Aging. 2001;18(9):685-716
references: 11599635
references: Antioxid Redox Signal. 2009 Mar;11(3):425-38
references: 19072199
references: Brain. 2005 Jul;128(Pt 7):1686-706
references: 15872021
references: Antioxid Redox Signal. 2009 Mar;11(3):669-702
references: 19014277
references: Science. 2003 Jan 10;299(5604):256-9
references: 12446870
references: Lancet Neurol. 2006 Jun;5(6):525-35
references: 16713924
references: Chem Res Toxicol. 2005 Dec;18(12):1917-26
references: 16359182
references: Am J Physiol. 1995 May;268(5 Pt 1):L699-722
references: 7762673
references: Biochem Biophys Res Commun. 1997 Feb 13;231(2):509-13
references: 9070310
references: Ann Neurol. 1998 Nov;44(5):819-24
references: 9818940
references: J Clin Invest. 2008 Feb;118(2):659-70
references: 18219391
references: J Neuropathol Exp Neurol. 2008 Nov;67(11):1055-62
references: 18957896
references: Clin Chim Acta. 1990 Jan 31;187(1):11-20
references: 2138526
references: J Biol Chem. 2009 May 22;284(21):14245-57
references: 19293155
references: Autophagy. 2011 May;7(5):531-2
references: 21317550
references: Cancer Prev Res (Phila). 2011 Oct;4(10):1665-74
references: 21803983
references: Free Radic Biol Med. 2000 Feb 1;28(3):463-99
references: 10699758
references: Neuroscience. 2013 Jun 25;241:80-8
references: 23523995
references: PLoS One. 2013;8(2):e56625
references: 23418589
references: J Signal Transduct. 2011;2011:792639
references: 21637379
references: Antioxid Redox Signal. 2011 Jun 15;14(12):2347-60
references: 21254817
references: Neurology. 2004 May 25;62(10):1758-65
references: 15159474
references: Antioxid Redox Signal. 2012 Nov 1;17(9):1277-330
references: 22413952
references: Brain Res. 2012 Mar 29;1446:109-18
references: 22353756
references: Nature. 2002 Dec 12;420(6916):629-35
references: 12478284
references: Ann Neurol. 2002 Oct;52(4):448-57
references: 12325074
references: J Mol Neurosci. 2009 Jun;38(2):94-102
references: 18712292
references: J Neurochem. 1997 Nov;69(5):2064-74
references: 9349552
references: Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11908-13
references: 12193649
references: Molecules. 2010 Oct 20;15(10):7266-91
references: 20966874
references: J Biol Chem. 2003 Aug 15;278(33):31372-9
references: 12761214
references: Ann Neurol. 1995 Oct;38(4):691-5
references: 7574472
references: Hum Mol Genet. 2012 Jul 1;21(13):3013-24
references: 22492997
references: Nature. 1993 Mar 4;362(6415):59-62
references: 8446170
references: Glia. 2000 Jan 1;29(1):25-34
references: 10594920
references: Eur J Pharmacol. 2013 Jan 5;698(1-3):6-18
references: 23123057
references: Hum Mol Genet. 2008 Nov 1;17(21):3357-67
references: 18689799
references: Biochem Soc Trans. 1993 May;21(2):367-70
references: 8359498
references: Antioxid Redox Signal. 2010 Dec 1;13(11):1699-712
references: 20486766
references: Chem Res Toxicol. 2012 Sep 17;25(9):1893-901
references: 22894569
references: J Neurosci. 2008 Dec 10;28(50):13574-81
references: 19074031
references: Front Biosci (Landmark Ed). 2009 Jan 01;14(4):1197-218
references: 19273125
references: Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):9103-8
references: 15181200
references: Lab Invest. 2013 Jul;93(7):825-33
references: 23711824
references: Neurotoxicology. 2012 Jun;33(3):272-9
references: 22342405
references: Int J Cell Biol. 2012;2012:908724
references: 22675362
references: Neurosci Lett. 2010 Jan 18;469(1):159-63
references: 19944739
references: Int J Dev Neurosci. 2010 Jun;28(4):289-95
references: 20362658
references: Oxid Med Cell Longev. 2012;2012:428010
references: 22685618
references: Free Radic Biol Med. 2011 Jul 1;51(1):88-96
references: 21457778
references: Acta Pharmacol Sin. 2006 Jul;27(7):821-6
references: 16787564
references: Acta Neuropathol. 2005 Aug;110(2):101-12
references: 15983830
references: Neurochem Res. 2006 Oct;31(10):1263-9
references: 17021948
references: J Neurochem. 2002 Feb;80(4):616-25
references: 11841569
references: Biochem Biophys Res Commun. 2013 Apr 19;433(4):602-6
references: 23537652
references: J Neurosci. 2007 Jul 18;27(29):7777-85
references: 17634371
references: Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9256-61
references: 12855764
references: Biol Chem. 2006 Oct-Nov;387(10-11):1405-10
references: 17081113
references: Ann Neurol. 1997 Oct;42(4):644-54
references: 9382477
references: Int J Mol Sci. 2012;13(8):10478-10504
references: 22949875
references: Hum Mol Genet. 2010 Oct 1;19(19):3734-46
references: 20639397
references: Free Radic Biol Med. 2012 Dec 1;53(11):2028-42
references: 23000247
references: Free Radic Biol Med. 2012 Aug 15;53(4):936-50
references: 22683601
references: J Neurochem. 2006 Jun;97(6):1634-58
references: 16805774
references: Neurochem Res. 2005 Aug;30(8):1003-7
references: 16258849
references: Cell Mol Life Sci. 2012 Jan;69(2):215-21
references: 21947442
references: J Biol Chem. 2002 Dec 6;277(49):47551-6
references: 12356748
references: Neurol Res Int. 2011;2011:458427
references: 21603028
references: Antioxid Redox Signal. 2008 Aug;10(8):1343-74
references: 18522489
references: J Bioenerg Biomembr. 2011 Dec;43(6):569-79
references: 22083126
references: Mediators Inflamm. 2012;2012:401264
references: 22544998
references: Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15091-6
references: 17015834
references: Nat Rev Neurosci. 2006 Sep;7(9):710-23
references: 16924260
references: Oxid Med Cell Longev. 2011;2011:467180
references: 22191013
references: Food Chem Toxicol. 2008 Apr;46(4):1271-8
references: 18082923
references: Neurol Res Int. 2012;2012:878030
references: 23050144
references: Biochemistry. 2008 Feb 5;47(5):1381-92
references: 18181649
references: Neurol Res Int. 2012;2012:278725
references: 22778949
references: Curr Neuropharmacol. 2012 Dec;10(4):321-7
references: 23730256
references: Neurobiol Dis. 2004 Feb;15(1):160-70
references: 14751781
references: Neurology. 1996 Oct;47(4):1060-4
references: 8857745
references: Neurosurg Focus. 2010 Jan;28(1):E7
references: 20043722
references: Eur J Neurosci. 2010 Mar;31(6):967-77
references: 20377612
references: FEBS Lett. 2003 Aug 14;549(1-3):171-5
references: 12914946
references: J Mol Biol. 2006 Mar 3;356(4):1036-48
references: 16403519
references: Molecules. 2010 Nov 03;15(11):7792-814
references: 21060289
references: J Neurosci. 1998 May 1;18(9):3241-50
references: 9547233
references: Biochem Biophys Res Commun. 2009 Jun 12;383(4):469-74
references: 19371728
references: Biochem Biophys Res Commun. 1998 Oct 20;251(2):545-9
references: 9792810
references: Free Radic Biol Med. 2010 Mar 1;48(5):629-41
references: 19969067
references: Indian J Clin Biochem. 2009 Jan;24(1):98-101
references: 23105815
references: Hippocampus. 2013 Jul;23(7):634-47
references: 23536494
references: J Neurol Sci. 2010 Jan 15;288(1-2):1-12
references: 19840884
references: Neurosci Lett. 2006 Mar 6;395(2):103-7
references: 16356650
references: J Biol Chem. 2011 Oct 7;286(40):35308-17
references: 21852238
references: Hum Mol Genet. 2011 Nov 1;20(21):4196-208
references: 21828072
references: Curr Neurovasc Res. 2012 Feb;9(1):32-41
references: 22272764
references: Ann Neurol. 1998 Oct;44(4):696-9
references: 9778272
references: Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):385-94
references: 15706085
references: Free Radic Biol Med. 2009 Jun 15;46(12):1574-80
references: 19298851
references: Pharmacol Res. 2008 May;57(5):325-31
references: 18455424
references: Oxid Med Cell Longev. 2012;2012:163913
references: 22619696
references: Antioxid Redox Signal. 2013 Jan 10;18(2):139-57
references: 22746536
references: J Neurochem. 2010 May;113(4):860-70
references: 20202083
references: J Bioenerg Biomembr. 2011 Dec;43(6):593-9
references: 22081209
references: Exp Neurobiol. 2013 Mar;22(1):11-7
references: 23585717
references: Prog Neurobiol. 2011 Mar;93(3):444-55
references: 21251953
references: Biochim Biophys Acta. 2006 Nov-Dec;1762(11-12):1051-67
references: 16713195
references: Biol Pharm Bull. 2011;34(8):1194-7
references: 21804205
references: J Neurosci Res. 2009 Jan;87(1):123-9
references: 18711745
references: Pharmacol Ther. 2010 Mar;125(3):376-93
references: 19945483
references: Free Radic Biol Med. 2013 Oct;63:1-29
references: 23567191
references: Science. 2004 May 21;304(5674):1120-2
references: 15155938
references: Exp Neurol. 2007 Sep;207(1):107-17
references: 17631292
references: Toxicology. 2004 Oct 1;202(3):213-25
references: 15337584
references: Neurosci Lett. 1995 Oct 20;199(2):152-4
references: 8584246
references: J Am Coll Nutr. 2009 Aug;28 Suppl:492S-499S
references: 20234037
references: Neuroscience. 2011 Nov 24;196:251-64
references: 21907265
references: PLoS One. 2013;8(3):e59843
references: 23555802