{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:13:43Z","timestamp":1792174423691,"version":"4.4.0"},"reference-count":195,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T00:00:00Z","timestamp":1630713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005888","name":"Uniwersytet Medyczny w Lodzi","doi-asserted-by":"publisher","award":["503\/0-079-04\/503-01-001"],"award-info":[{"award-number":["503\/0-079-04\/503-01-001"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005888","name":"Uniwersytet Medyczny w Lodzi","doi-asserted-by":"publisher","award":["502-03\/0-079-04\/502-04-035"],"award-info":[{"award-number":["502-03\/0-079-04\/502-04-035"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nrf2 is a basic region leucine-zipper transcription factor that plays a pivotal role in the coordinated gene expression of antioxidant and detoxifying enzymes, promoting cell survival in adverse environmental or defective metabolic conditions. After synthesis, Nrf2 is arrested in the cytoplasm by the Kelch-like ECH-associated protein 1 suppressor (Keap1) leading Nrf2 to ubiquitin-dependent degradation. One Nrf2 activation mechanism relies on disconnection from the Keap1 homodimer through the oxidation of cysteine at specific sites of Keap1. Free Nrf2 enters the nucleus, dimerizes with small musculoaponeurotic fibrosarcoma proteins (sMafs), and binds to the antioxidant response element (ARE) sequence of the target genes. Since oxidative stress, next to neuroinflammation and mitochondrial dysfunction, is one of the hallmarks of neurodegenerative pathologies, a molecular intervention into Nrf2\/ARE signaling and the enhancement of the transcriptional activity of particular genes are targets for prevention or delaying the onset of age-related and inherited neurogenerative diseases. In this study, we review evidence for the Nrf2\/ARE-driven pathway dysfunctions leading to various neurological pathologies, such as Alzheimer\u2019s, Parkinson\u2019s, and Huntington\u2019s diseases, as well as amyotrophic lateral sclerosis, and the beneficial role of natural and synthetic molecules that are able to interact with Nrf2 to enhance its protective efficacy.<\/jats:p>","DOI":"10.3390\/ijms22179592","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T13:15:56Z","timestamp":1630934156000},"page":"9592","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":195,"title":["An Overview of the Nrf2\/ARE Pathway and Its Role in Neurodegenerative Diseases"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5411-3778","authenticated-orcid":false,"given":"Emilia","family":"Zgorzynska","sequence":"first","affiliation":[{"name":"Department of Cell-to-Cell Communication, Medical University of Lodz, Mazowiecka 6\/8, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4122-4882","authenticated-orcid":false,"given":"Barbara","family":"Dziedzic","sequence":"additional","affiliation":[{"name":"Department of Cell-to-Cell Communication, Medical University of Lodz, Mazowiecka 6\/8, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Walczewska","sequence":"additional","affiliation":[{"name":"Department of Cell-to-Cell Communication, Medical University of Lodz, Mazowiecka 6\/8, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1016\/j.bbagrm.2015.08.001","article-title":"Changing gears in Nrf1 research, from mechanisms of regulation to its role in disease and prevention","volume":"1849","author":"Bugno","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"10228","DOI":"10.1093\/nar\/gks827","article-title":"Nrf2-MafG heterodimers contribute globally to antioxidant and metabolic networks","volume":"40","author":"Hirotsu","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.ccr.2012.05.016","article-title":"Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming","volume":"22","author":"Mitsuishi","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1242\/bio.20134853","article-title":"Nrf2 impacts cellular bioenergetics by controlling substrate availability for mitochondrial respiration","volume":"2","author":"Baird","year":"2013","journal-title":"Biol. Open"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.tips.2013.04.005","article-title":"Toward clinical application of the Keap1-Nrf2 pathway","volume":"34","author":"Suzuki","year":"2013","journal-title":"Trends Pharm. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1006\/bbrc.1997.6943","article-title":"An Nrf2\/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements","volume":"236","author":"Itoh","year":"1997","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_7","first-page":"3299","article-title":"The Cap\u2019n\u2019Collar 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","volume":"61","author":"McMahon","year":"2001","journal-title":"Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"32485","DOI":"10.1074\/jbc.M503074200","article-title":"Nrf2 controls constitutive and inducible expression of ARE-driven genes through a dynamic pathway involving nucleocytoplasmic shuttling by Keap1","volume":"280","author":"Nguyen","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1159\/000491465","article-title":"Nrf2 pathway in age-related neurological disorders: Insights into MicroRNAs","volume":"47","author":"Paladino","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.freeradbiomed.2014.03.009","article-title":"Luteolin provides neuroprotection in models of traumatic brain injury via the Nrf2-ARE pathway","volume":"71","author":"Xu","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.tibs.2014.02.002","article-title":"The Nrf2 regulatory network provides an interface between redox and intermediary metabolism","volume":"39","author":"Hayes","year":"2014","journal-title":"Trends Biochem. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"14636","DOI":"10.1096\/fj.201901930R","article-title":"Post-transcriptional regulation of Nrf2-mRNA by the mRNA-binding proteins HuR and AUF1","volume":"33","author":"Poganik","year":"2019","journal-title":"FASEB J."},{"key":"ref_13","unstructured":"The National Center for Biotechnology Information, NCBI (2021, August 16). Available online: https:\/\/www.ncbi.nlm.nih.gov\/gene\/4780\/."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1016\/j.celrep.2016.08.010","article-title":"Recurrent Loss of NFE2L2 Exon 2 Is a Mechanism for Nrf2 Pathway Activation in Human Cancers","volume":"16","author":"Goldstein","year":"2016","journal-title":"Cell Rep."},{"key":"ref_15","unstructured":"(2021, August 16). UniProt Consortium. Available online: https:\/\/www.uniprot.org\/uniprot\/Q16236."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2883","DOI":"10.1128\/MCB.22.9.2883-2892.2002","article-title":"Enhanced expression of the transcription factor Nrf2 by cancer chemopreventive agents: Role of antioxidant response element-like sequences in the nrf2 promoter","volume":"22","author":"Kwak","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"He, F., Ru, X., and Wen, T. (2020). NRF2, a transcription factor for stress response and beyond. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134777"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"20340","DOI":"10.1074\/jbc.M412081200","article-title":"Transcriptional regulation of NF-E2 p45-related factor (NRF2) expression by the aryl hydrocarbon receptor-xenobiotic response element signaling pathway: Direct cross-talk between phase I and II drug-metabolizing enzymes","volume":"280","author":"Miao","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"13943","DOI":"10.1073\/pnas.93.24.13943","article-title":"NRF2, a member of the NFE2 family of transcription factors, is not essential for murine erythropoiesis, growth, and development","volume":"93","author":"Chan","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Yu, S., Khor, T.O., Cheung, K.L., Li, W., Wu, T.Y., Huang, Y., Foster, B.A., Kan, Y.W., and Kong, A.N. (2010). Nrf2 expression is regulated by epigenetic mechanisms in prostate cancer of TRAMP mice. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0008579"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.cotox.2016.10.008","article-title":"Regulation of Keap1-Nrf2 signaling: The role of epigenetics","volume":"1","author":"Cheng","year":"2016","journal-title":"Curr. Opin. Toxicol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Manolakou, S.D., Ziros, P.G., and Sykiotis, G.P. (2017). NFE2L2 (nuclear factor, erythroid 2-like 2). Atlas Genet. Cytogenet. Oncol. Haematol., 2.","DOI":"10.4267\/2042\/62259"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5188","DOI":"10.1182\/blood-2012-04-422121","article-title":"The high Nrf2 expression in human acute myeloid leukemia is driven by NF-\u03baB and underlies its chemo-resistance","volume":"120","author":"Rushworth","year":"2012","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1186\/gb-2005-6-13-246","article-title":"The AP-2 family of transcription factors","volume":"6","author":"Eckert","year":"2005","journal-title":"Genome Biol"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nature10189","article-title":"Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis","volume":"475","author":"DeNicola","year":"2011","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5835","DOI":"10.1158\/1078-0432.CCR-12-3629","article-title":"Molecular Pathways: Targeting MYC-induced metabolic reprogramming and oncogenic stress in cancer","volume":"19","author":"Li","year":"2013","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.humpath.2006.01.022","article-title":"c-Jun activation is associated with proliferation and angiogenesis in invasive breast cancer","volume":"37","author":"Vleugel","year":"2006","journal-title":"Hum. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1093\/carcin\/bgn095","article-title":"Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2","volume":"29","author":"Wang","year":"2008","journal-title":"Carcinogenesis"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7430","DOI":"10.1158\/0008-5472.CAN-14-1439","article-title":"Oncogenic KRAS confers chemoresistance by upregulating NRF2","volume":"74","author":"Tao","year":"2014","journal-title":"Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"14654","DOI":"10.1074\/jbc.M601613200","article-title":"BRCA1 modulates xenobiotic stress-inducible gene expression by interacting with ARNT in human breast cancer cells","volume":"281","author":"Kang","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.redox.2018.06.012","article-title":"Breast cancer susceptibility protein 1 (BRCA1) rescues neurons from cerebral ischemia\/reperfusion injury through NRF2-mediated antioxidant pathway","volume":"18","author":"Xu","year":"2018","journal-title":"Redox Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"41692","DOI":"10.18632\/oncotarget.6150","article-title":"Mutant p53 confers chemoresistance in non-small cell lung cancer by upregulating Nrf2","volume":"6","author":"Tung","year":"2015","journal-title":"Oncotarget"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3597","DOI":"10.1523\/JNEUROSCI.23-09-03597.2003","article-title":"Sp1 and Sp3 are oxidative stress-inducible, antideath transcription factors in cortical neurons","volume":"23","author":"Ryu","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_34","first-page":"5456","article-title":"MiR-93 inhibition ameliorates OGD\/R induced cardiomyocyte apoptosis by targeting Nrf2","volume":"21","author":"Yan","year":"2017","journal-title":"Eur. Rev. Med. Pharmacol. Sci"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s10577-019-09608-y","article-title":"MiR-153 regulates cardiomyocyte apoptosis by targeting Nrf2\/HO-1 signaling","volume":"27","author":"Zhu","year":"2019","journal-title":"Chromosom. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"136.e1","DOI":"10.1016\/j.ajog.2017.10.040","article-title":"Oxidative stress-induced miR-27a targets the redox gene nuclear factor erythroid 2-related factor 2 in diabetic embryopathy","volume":"218","author":"Zhao","year":"2018","journal-title":"Am. J. Obs. Gynecol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"101336","DOI":"10.1016\/j.redox.2019.101336","article-title":"Inhibiting microRNA-144 potentiates Nrf2-dependent antioxidant signaling in RPE and protects against oxidative stress-induced outer retinal degeneration","volume":"28","author":"Jadeja","year":"2020","journal-title":"Redox Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1016\/j.biocel.2009.09.016","article-title":"The complexities of microRNA regulation: Mirandering around the rules","volume":"42","author":"Breving","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4338","DOI":"10.1182\/blood-2009-04-214817","article-title":"microRNA miR-144 modulates oxidative stress tolerance and associates with anemia severity in sickle cell disease","volume":"116","author":"Sangokoya","year":"2010","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1007\/s10549-011-1604-1","article-title":"MiR-28 regulates Nrf2 expression through a Keap1-independent mechanism","volume":"129","author":"Yang","year":"2011","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Narasimhan, M., Patel, D., Vedpathak, D., Rathinam, M., Henderson, G., and Mahimainathan, L. (2012). Identification of novel microRNAs in post-transcriptional control of Nrf2 expression and redox homeostasis in neuronal, SH-SY5Y cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051111"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1515\/tnsci-2020-0172","article-title":"miR-380-5p facilitates NRF2 and attenuates cerebral ischemia\/reperfusion injury-induced neuronal cell death by directly targeting BACH1","volume":"12","author":"Wang","year":"2021","journal-title":"Transl. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.bbrc.2019.07.012","article-title":"MicroRNA-152-3p protects neurons from oxygen-glucose-deprivation\/reoxygenation-induced injury through upregulation of Nrf2\/ARE antioxidant signaling by targeting PSD-93","volume":"517","author":"Zhang","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"31556","DOI":"10.1074\/jbc.M403061200","article-title":"Redox-regulated turnover of Nrf2 is determined by at least two separate protein domains, the redox-sensitive Neh2 degron and the redox-insensitive Neh6 degron","volume":"279","author":"McMahon","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"10895","DOI":"10.1128\/MCB.25.24.10895-10906.2005","article-title":"The carboxy-terminal Neh3 domain of Nrf2 is required for transcriptional activation","volume":"25","author":"Nioi","year":"2005","journal-title":"Mol. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1128\/MCB.01639-08","article-title":"Acetylation of Nrf2 by p300\/CBP augments promoter-specific DNA binding of Nrf2 during the antioxidant response","volume":"29","author":"Sun","year":"2009","journal-title":"Mol. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3097","DOI":"10.1158\/0008-5472.CAN-12-3386","article-title":"RXR\u03b1 inhibits the NRF2-ARE signaling pathway through a direct interaction with the Neh7 domain of NRF2","volume":"73","author":"Wang","year":"2013","journal-title":"Cancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"F743","DOI":"10.1152\/ajprenal.00376.2002","article-title":"Heme activates the heme oxygenase-1 gene in renal epithelial cells by stabilizing Nrf2","volume":"284","author":"Alam","year":"2003","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1046\/j.1365-2443.2003.00640.x","article-title":"Keap1 regulates both cytoplasmic-nuclear shuttling and degradation of Nrf2 in response to electrophiles","volume":"8","author":"Itoh","year":"2003","journal-title":"Genes Cells"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3605","DOI":"10.1038\/sj.emboj.7601243","article-title":"Structure of the Keap1:Nrf2 interface provides mechanistic insight into Nrf2 signaling","volume":"25","author":"Lo","year":"2006","journal-title":"EMBO J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"re3","DOI":"10.1126\/scisignal.3112re3","article-title":"Stress-activated cap\u2019n\u2019collar transcription factors in aging and human disease","volume":"3","author":"Sykiotis","year":"2010","journal-title":"Sci. Signal."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3100","DOI":"10.1128\/MCB.00389-16","article-title":"Absolute Amounts and Status of the Nrf2-Keap1-Cul3 Complex within Cells","volume":"36","author":"Iso","year":"2016","journal-title":"Mol. Cell. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1158\/0008-5472.CAN-12-4400","article-title":"Proteomic analysis of ubiquitin ligase KEAP1 reveals associated proteins that inhibit NRF2 ubiquitination","volume":"73","author":"Hast","year":"2013","journal-title":"Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.molcel.2009.04.029","article-title":"Direct interaction between Nrf2 and p21(Cip1\/WAF1) upregulates the Nrf2-mediated antioxidant response","volume":"34","author":"Chen","year":"2009","journal-title":"Mol. Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3765","DOI":"10.1038\/onc.2012.388","article-title":"Nrf2 is controlled by two distinct \u03b2-TrCP recognition motifs in its Neh6 domain, one of which can be modulated by GSK-3 activity","volume":"32","author":"Chowdhry","year":"2013","journal-title":"Oncogene"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1089\/ars.2014.5843","article-title":"The PTEN\/NRF2 axis promotes human carcinogenesis","volume":"21","author":"Rojo","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1042\/BST20150011","article-title":"Dual regulation of transcription factor Nrf2 by Keap1 and by the combined actions of \u03b2-TrCP and GSK-3","volume":"43","author":"Hayes","year":"2015","journal-title":"Biochem. Soc. Trans."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"12132","DOI":"10.1074\/jbc.M511198200","article-title":"Phosphorylation of tyrosine 568 controls nuclear export of Nrf2","volume":"281","author":"Jain","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"16502","DOI":"10.1074\/jbc.M611336200","article-title":"GSK-3beta acts upstream of Fyn kinase in regulation of nuclear export and degradation of NF-E2 related factor 2","volume":"282","author":"Jain","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1101\/gad.238246.114","article-title":"Hrd1 suppresses Nrf2-mediated cellular protection during liver cirrhosis","volume":"28","author":"Wu","year":"2014","journal-title":"Genes Dev."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Lo, J.Y., Spatola, B.N., and Curran, S.P. (2017). WDR23 regulates NRF2 independently of KEAP1. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1006762"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"11783","DOI":"10.1038\/s41598-019-48286-y","article-title":"Nuclear and cytoplasmic WDR-23 isoforms mediate differential effects on GEN-1 and SKN-1 substrates","volume":"9","author":"Spatola","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"44675","DOI":"10.1074\/jbc.M307633200","article-title":"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 elemen","volume":"278","author":"Bloom","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1002\/jbt.20212","article-title":"Phosphorylation of Nrf2 in the transcription activation domain by casein kinase 2 (CK2) is critical for the nuclear translocation and transcription activation function of Nrf2 in IMR-32 neuroblastoma cells","volume":"22","author":"Apopa","year":"2008","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.cmet.2018.02.006","article-title":"Synergy between the KEAP1\/NRF2 and PI3K Pathways Drives Non-Small-Cell Lung Cancer with an Altered Immune Microenvironment","volume":"27","author":"Best","year":"2018","journal-title":"Cell Metab."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1128\/MCB.00118-16","article-title":"AMPK Facilitates Nuclear Accumulation of Nrf2 by Phosphorylating at Serine 550","volume":"36","author":"Joo","year":"2016","journal-title":"Mol. Cell. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1089\/ars.2017.7342","article-title":"Transcriptional Regulation by Nrf2","volume":"29","author":"Tonelli","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1128\/MCB.23.4.1163-1174.2003","article-title":"Small Maf compound mutants display central nervous system neuronal degeneration, aberrant transcription, and Bach protein mislocalization coincident with myoclonus and abnormal startle response","volume":"23","author":"Katsuoka","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"7074","DOI":"10.1093\/nar\/gkm638","article-title":"Heme oxygenase-1 induction by NRF2 requires inactivation of the transcriptional repressor BACH1","volume":"35","author":"Reichard","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"16891","DOI":"10.1074\/jbc.M500166200","article-title":"Bach1 competes with Nrf2 leading to negative regulation of the antioxidant response element (ARE)-mediated NAD(P)H:quinone oxidoreductase 1 gene expression and induction in response to antioxidants","volume":"280","author":"Dhakshinamoorthy","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5734","DOI":"10.1093\/emboj\/17.19.5734","article-title":"Identification of Bach2 as a B-cell-specific partner for small maf proteins that negatively regulate the immunoglobulin heavy chain gene 3\u2032 enhancer","volume":"17","author":"Muto","year":"1998","journal-title":"EMBO J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1046\/j.1365-2443.2001.00469.x","article-title":"Two domains of Nrf2 cooperatively bind CBP, a CREB binding protein, and synergistically activate transcription","volume":"6","author":"Katoh","year":"2001","journal-title":"Genes Cells"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1006\/bbrc.2001.5944","article-title":"Functional characterization of transcription regulators that interact with the electrophile response element","volume":"289","author":"Zhu","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.bbamcr.2008.01.002","article-title":"NF-kappaB\/p65 antagonizes Nrf2-ARE pathway by depriving CBP from Nrf2 and facilitating recruitment of HDAC3 to MafK","volume":"1783","author":"Liu","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"483","DOI":"10.3390\/cancers2020483","article-title":"Nrf2 and NF-\u03baB and Their Concerted Modulation in Cancer Pathogenesis and Progression","volume":"2","author":"Bellezza","year":"2010","journal-title":"Cancers"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1128\/MCB.00785-15","article-title":"The Mediator Subunit MED16 Transduces NRF2-Activating Signals into Antioxidant Gene Expression","volume":"36","author":"Sekine","year":"2016","journal-title":"Mol. Cell. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.1038\/sj.onc.1202237","article-title":"Nrf2 and Nrf1 in association with Jun proteins regulate antioxidant response element-mediated expression and coordinated induction of genes encoding detoxifying enzymes","volume":"17","author":"Venugopal","year":"1998","journal-title":"Oncogene"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Sarcinelli, C., Dragic, H., Piecyk, M., Barbet, V., Duret, C., Barthelaix, A., Ferraro-Peyret, C., Fauvre, J., Renno, T., and Chaveroux, C. (2020). ATF4-Dependent. Cancers, 12.","DOI":"10.3390\/cancers12030569"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1158\/0008-5472.CAN-07-2170","article-title":"Activating transcription factor 3 is a novel repressor of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2)-regulated stress pathway","volume":"68","author":"Brown","year":"2008","journal-title":"Cancer Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"18015","DOI":"10.1074\/jbc.M600603200","article-title":"Nrf2 negatively regulates osteoblast differentiation via interfering with Runx2-dependent transcriptional activation","volume":"281","author":"Hinoi","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1007\/s00018-010-0336-4","article-title":"NF-E2-related factor 2, a key inducer of antioxidant defenses, negatively regulates the CFTR transcription","volume":"67","author":"Lopez","year":"2010","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"E10352","DOI":"10.1073\/pnas.1812125115","article-title":"RPA1 binding to NRF2 switches ARE-dependent transcriptional activation to ARE-NRE-dependent repression","volume":"115","author":"Liu","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1042\/bj20020320","article-title":"Loss of the Nrf2 transcription factor causes a marked reduction in constitutive and inducible expression of the glutathione S-transferase Gsta1, Gsta2, Gstm1, Gstm2, Gstm3 and Gstm4 genes in the livers of male and female mice","volume":"365","author":"Chanas","year":"2002","journal-title":"Biochem. J."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1042\/BJ20051518","article-title":"Role of Nrf2 in the regulation of the Mrp2 (ABCC2) gene","volume":"395","author":"Vollrath","year":"2006","journal-title":"Biochem. J."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.taap.2009.03.005","article-title":"Transcription factor Nrf2 mediates an adaptive response to sulforaphane that protects fibroblasts in vitro against the cytotoxic effects of electrophiles, peroxides and redox-cycling agents","volume":"237","author":"Higgins","year":"2009","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1089\/ars.2011.4391","article-title":"The cystine\/glutamate antiporter system x(c)(-) in health and disease: From molecular mechanisms to novel therapeutic opportunities","volume":"18","author":"Lewerenz","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1093\/toxsci\/kfr183","article-title":"Beneficial role of Nrf2 in regulating NADPH generation and consumption","volume":"123","author":"Wu","year":"2011","journal-title":"Toxicol. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.bbagen.2013.09.013","article-title":"Regulation of the human thioredoxin gene promoter and its key substrates: A study of functional and putative regulatory elements","volume":"1840","author":"Hawkes","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.mrfmmm.2015.06.007","article-title":"Nrf2 facilitates repair of radiation induced DNA damage through homologous recombination repair pathway in a ROS independent manner in cancer cells","volume":"779","author":"Jayakumar","year":"2015","journal-title":"Mutat. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"9109","DOI":"10.1093\/nar\/gkaa631","article-title":"NRF2 preserves genomic integrity by facilitating ATR activation and G2 cell cycle arrest","volume":"48","author":"Sun","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1080\/15548627.2016.1208889","article-title":"Transcription factor NFE2L2\/NRF2 is a regulator of macroautophagy genes","volume":"12","author":"Pajares","year":"2016","journal-title":"Autophagy"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.freeradbiomed.2013.04.007","article-title":"The transcription factor Nrf2 promotes survival by enhancing the expression of uncoupling protein 3 under conditions of oxidative stress","volume":"61","author":"Anedda","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1161\/01.RES.0000338597.71702.ad","article-title":"Heme oxygenase-1 regulates cardiac mitochondrial biogenesis via Nrf2-mediated transcriptional control of nuclear respiratory factor-1","volume":"103","author":"Piantadosi","year":"2008","journal-title":"Circ. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1152\/physrev.00025.2007","article-title":"Transcriptional paradigms in mammalian mitochondrial biogenesis and function","volume":"88","author":"Scarpulla","year":"2008","journal-title":"Physiol. Rev."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Singh, A., Kukreti, R., Saso, L., and Kukreti, S. (2019). Oxidative Stress: A Key Modulator in Neurodegenerative Diseases. Molecules, 24.","DOI":"10.3390\/molecules24081583"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"247","DOI":"10.3389\/fncel.2020.00247","article-title":"PHF-Core Tau as the Potential Initiating Event for Tau Pathology in Alzheimer\u2019s Disease","volume":"14","author":"Harrington","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1212\/WNL.52.6.1158","article-title":"The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer\u2019s disease","volume":"52","author":"Delacourte","year":"1999","journal-title":"Neurology"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"595","DOI":"10.15252\/emmm.201606210","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease at 25 years","volume":"8","author":"Selkoe","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/nrn2967","article-title":"Amyloid-\u03b2 and tau--a toxic pas de deux in Alzheimer\u2019s disease","volume":"12","author":"Ittner","year":"2011","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"12516","DOI":"10.1073\/pnas.1819541116","article-title":"NRF2\/ARE pathway negatively regulates BACE1 expression and ameliorates cognitive deficits in mouse Alzheimer\u2019s models","volume":"116","author":"Bahn","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3389\/fneur.2013.00083","article-title":"The importance of tau phosphorylation for neurodegenerative diseases","volume":"4","author":"Noble","year":"2013","journal-title":"Front. Neurol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1016\/j.neurobiolaging.2005.06.004","article-title":"Increased levels of 4-hydroxynonenal and acrolein, neurotoxic markers of lipid peroxidation, in the brain in Mild Cognitive Impairment and early Alzheimer\u2019s disease","volume":"27","author":"Williams","year":"2006","journal-title":"Neurobiol. Aging"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1006\/exnr.1997.6750","article-title":"Increased peroxidation and reduced antioxidant enzyme activity in Alzheimer\u2019s disease","volume":"150","author":"Marcus","year":"1998","journal-title":"Exp. Neurol."},{"key":"ref_104","first-page":"529","article-title":"Urinary 8-hydroxy-2\u2032-deoxyguanosine level and plasma paraoxonase 1 activity with Alzheimer\u2019s disease","volume":"50","author":"Zengi","year":"2011","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3050971","DOI":"10.1155\/2020\/3050971","article-title":"Nrf2 Ablation Promotes Alzheimer\u2019s Disease-Like Pathology in APP\/PS1 Transgenic Mice: The Role of Neuroinflammation and Oxidative Stress","volume":"2020","author":"Ren","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.redox.2017.07.006","article-title":"NRF2 deficiency replicates transcriptomic changes in Alzheimer\u2019s patients and worsens APP and TAU pathology","volume":"13","author":"Rojo","year":"2017","journal-title":"Redox Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/S0197-4580(00)00114-7","article-title":"NAD(P)H:quinone oxidoreductase activity is increased in hippocampal pyramidal neurons of patients with Aalzheimer\u2019s disease","volume":"21","author":"Wang","year":"2000","journal-title":"Neurobiol. Aging"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1002\/ana.410370609","article-title":"Expression of heme oxygenase-1 in the senescent and Alzheimer-diseased brain","volume":"37","author":"Schipper","year":"1995","journal-title":"Ann. Neurol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1097\/nen.0b013e31802d6da9","article-title":"Expression of Nrf2 in neurodegenerative diseases","volume":"66","author":"Ramsey","year":"2007","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.mad.2009.12.007","article-title":"Nrf2-encoding NFE2L2 haplotypes influence disease progression but not risk in Alzheimer\u2019s disease and age-related cataract","volume":"131","author":"Landgren","year":"2010","journal-title":"Mech. Ageing Dev."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"9090","DOI":"10.1523\/JNEUROSCI.1357-09.2009","article-title":"Impaired balance of mitochondrial fission and fusion in Alzheimer\u2019s disease","volume":"29","author":"Wang","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"614","DOI":"10.4161\/auto.4872","article-title":"Increased autophagic degradation of mitochondria in Alzheimer disease","volume":"3","author":"Moreira","year":"2007","journal-title":"Autophagy"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2013.03.018","article-title":"Mitochondrial diseases of the brain","volume":"63","author":"Chaturvedi","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1093\/hmg\/ddy042","article-title":"Hippocampal mutant APP and amyloid beta-induced cognitive decline, dendritic spine loss, defective autophagy, mitophagy and mitochondrial abnormalities in a mouse model of Alzheimer\u2019s disease","volume":"27","author":"Manczak","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.cotox.2016.10.002","article-title":"The multifaceted role of Nrf2 in mitochondrial function","volume":"1","author":"Kostov","year":"2016","journal-title":"Curr. Opin. Toxicol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.mcn.2008.07.010","article-title":"Nuclear factor erythroid 2-related factor 2 protects against beta amyloid","volume":"39","author":"Kanninen","year":"2008","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.biochi.2009.12.001","article-title":"Stabilization of transcription factor Nrf2 by tBHQ prevents oxidative stress-induced amyloid beta formation in NT2N neurons","volume":"92","author":"Eftekharzadeh","year":"2010","journal-title":"Biochimie"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"767","DOI":"10.3233\/JAD-2011-110512","article-title":"Therapeutic potential and anti-amyloidosis mechanisms of tert-butylhydroquinone for Alzheimer\u2019s disease","volume":"26","author":"Akhter","year":"2011","journal-title":"J. Alzheimers Dis."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"16505","DOI":"10.1073\/pnas.0908397106","article-title":"Intrahippocampal injection of a lentiviral vector expressing Nrf2 improves spatial learning in a mouse model of Alzheimer\u2019s disease","volume":"106","author":"Kanninen","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"22576","DOI":"10.1074\/jbc.M110.118976","article-title":"p62\/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription","volume":"285","author":"Jain","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"3496","DOI":"10.1038\/ncomms4496","article-title":"Nrf2 reduces levels of phosphorylated tau protein by inducing autophagy adaptor protein NDP52","volume":"5","author":"Jo","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s11064-017-2421-7","article-title":"Resveratrol Attenuates the Cytotoxicity Induced by Amyloid-\u03b2","volume":"43","author":"Hui","year":"2018","journal-title":"Neurochem. Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3233\/JAD-131031","article-title":"Optical and SPION-enhanced MR imaging shows that trans-stilbene inhibitors of NF-\u03baB concomitantly lower Alzheimer\u2019s disease plaque formation and microglial activation in A\u03b2PP\/PS-1 transgenic mouse brain","volume":"40","author":"Solberg","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1007\/s11357-012-9489-4","article-title":"Dietary resveratrol prevents Alzheimer\u2019s markers and increases life span in SAMP8","volume":"35","author":"Porquet","year":"2013","journal-title":"Age"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1177\/0269881114552744","article-title":"Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population","volume":"29","author":"Cox","year":"2015","journal-title":"J. Psychopharmacol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/alzrt146","article-title":"Oral curcumin for Alzheimer\u2019s disease: Tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study","volume":"4","author":"Ringman","year":"2012","journal-title":"Alzheimers Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-016-0779-0","article-title":"Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer\u2019s disease","volume":"14","author":"Moussa","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_128","first-page":"609","article-title":"A randomized, double-blind, placebo-controlled trial of resveratrol with glucose and malate (RGM) to slow the progression of Alzheimer\u2019s disease: A pilot study","volume":"4","author":"Zhu","year":"2018","journal-title":"Alzheimers Dement."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1021\/mp700113r","article-title":"Bioavailability of curcumin: Problems and promises","volume":"4","author":"Anand","year":"2007","journal-title":"Mol. Pharm."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1124\/dmd.104.000885","article-title":"High absorption but very low bioavailability of oral resveratrol in humans","volume":"32","author":"Walle","year":"2004","journal-title":"Drug Metab. Dispos."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"502","DOI":"10.2174\/1389202914666131210205839","article-title":"Mutations in PRKN and SNCA Genes Important for the Progress of Parkinson\u2019s Disease","volume":"14","author":"Oczkowska","year":"2013","journal-title":"Curr. Genom."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Brandes, M.S., and Gray, N.E. (2020). NRF2 as a Therapeutic Target in Neurodegenerative Diseases. ASN Neuro, 12.","DOI":"10.1177\/1759091419899782"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"236","DOI":"10.3389\/fnmol.2018.00236","article-title":"Oxidative Stress in Parkinson\u2019s Disease: A Systematic Review and Meta-Analysis","volume":"11","author":"Wei","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"8590578","DOI":"10.1155\/2016\/8590578","article-title":"The Role of Reactive Oxygen Species in the Pathogenesis of Alzheimer\u2019s Disease, Parkinson\u2019s Disease, and Huntington\u2019s Disease: A Mini Review","volume":"2016","author":"Manoharan","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3389\/fnana.2015.00091","article-title":"Oxidative stress and Parkinson\u2019s disease","volume":"9","author":"Blesa","year":"2015","journal-title":"Front. Neuroanat."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.tiv.2017.10.020","article-title":"A multi-biomarker analysis of the antioxidant efficacy of Parkinson\u2019s disease therapy","volume":"47","author":"Colamartino","year":"2018","journal-title":"Toxicol. In Vitro"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2933","DOI":"10.1073\/pnas.0813361106","article-title":"Nrf2-mediated neuroprotection in the MPTP mouse model of Parkinson\u2019s disease: Critical role for the astrocyte","volume":"106","author":"Chen","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1002\/glia.20947","article-title":"Nrf2 regulates microglial dynamics and neuroinflammation in experimental Parkinson\u2019s disease","volume":"58","author":"Rojo","year":"2010","journal-title":"Glia"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"3173","DOI":"10.1093\/hmg\/dds143","article-title":"\u03b1-Synuclein expression and Nrf2 deficiency cooperate to aggravate protein aggregation, neuronal death and inflammation in early-stage Parkinson\u2019s disease","volume":"21","author":"Ulusoy","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.3233\/JAD-161032","article-title":"Meta-Analysis of Parkinson\u2019s Disease and Alzheimer\u2019s Disease Revealed Commonly Impaired Pathways and Dysregulation of NRF2-Dependent Genes","volume":"56","author":"Wang","year":"2017","journal-title":"J. Alzheimers. Dis."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.neuro.2012.01.015","article-title":"Activation of the Nrf2-ARE pathway by siRNA knockdown of Keap1 reduces oxidative stress and provides partial protection from MPTP-mediated neurotoxicity","volume":"33","author":"Williamson","year":"2012","journal-title":"Neurotoxicology"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.biocel.2013.02.012","article-title":"Role of \u03b1-synuclein aggregation and the nuclear factor E2-related factor 2\/heme oxygenase-1 pathway in iron-induced neurotoxicity","volume":"45","author":"He","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.neuropharm.2013.11.026","article-title":"Naringenin protects against 6-OHDA-induced neurotoxicity via activation of the Nrf2\/ARE signaling pathway","volume":"79","author":"Lou","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.biopha.2015.07.034","article-title":"Schisandrin B shows neuroprotective effect in 6-OHDA-induced Parkinson\u2019s disease via inhibiting the negative modulation of miR-34a on Nrf2 pathway","volume":"75","author":"Ba","year":"2015","journal-title":"Biomed. Pharm."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.jnutbio.2011.02.004","article-title":"Sulforaphane, a natural constituent of broccoli, prevents cell death and inflammation in nephropathy","volume":"23","author":"Mukhopadhyay","year":"2012","journal-title":"J. Nutr. Biochem."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1021\/tx0502138","article-title":"Identification of sensor cysteines in human Keap1 modified by the cancer chemopreventive agent sulforaphane","volume":"18","author":"Hong","year":"2005","journal-title":"Chem. Res. Toxicol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.jnutbio.2014.12.008","article-title":"Sulforaphane attenuation of experimental diabetic nephropathy involves GSK-3 beta\/Fyn\/Nrf2 signaling pathway","volume":"26","author":"Shang","year":"2015","journal-title":"J. Nutr. Biochem."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"107989","DOI":"10.1016\/j.neuropharm.2020.107989","article-title":"Nrf2 activator via interference of Nrf2-Keap1 interaction has antioxidant and anti-inflammatory properties in Parkinson\u2019s disease animal model","volume":"167","author":"Kim","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"2728","DOI":"10.1021\/acschemneuro.0c00363","article-title":"Novel Curcumin-Diethyl Fumarate Hybrid as a Dualistic GSK-3\u03b2 Inhibitor\/Nrf2 Inducer for the Treatment of Parkinson\u2019s Disease","volume":"11","author":"Pruccoli","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1089\/ars.2006.8.2061","article-title":"Oxidative damage in Huntington\u2019s disease pathogenesis","volume":"8","author":"Browne","year":"2006","journal-title":"Antioxid. Redox Signal."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.bbrc.2007.05.093","article-title":"Increased oxidative damage and mitochondrial abnormalities in the peripheral blood of Huntington\u2019s disease patients","volume":"359","author":"Chen","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1007\/s00415-007-0611-y","article-title":"Oxidative stress parameters in plasma of Huntington\u2019s disease patients, asymptomatic Huntington\u2019s disease gene carriers and healthy subjects: A cross-sectional study","volume":"254","author":"Klepac","year":"2007","journal-title":"J. Neurol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s00401-010-0788-5","article-title":"Modulation of lipid peroxidation and mitochondrial function improves neuropathology in Huntington\u2019s disease mice","volume":"121","author":"Lee","year":"2011","journal-title":"Acta Neuropathol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/S0006-8993(00)02082-5","article-title":"Striatal oxidative damage parallels the expression of a neurological phenotype in mice transgenic for the mutation of Huntington\u2019s disease","volume":"862","author":"Segovia","year":"2000","journal-title":"Brain Res."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Jin, Y.N., Yu, Y.V., Gundemir, S., Jo, C., Cui, M., Tieu, K., and Johnson, G.V.W. (2013). Impaired mitochondrial dynamics and Nrf2 signaling contribute to compromised responses to oxidative stress in striatal cells expressing full-length mutant huntingtin. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0057932"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/35099568","article-title":"Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila","volume":"413","author":"Steffan","year":"2001","journal-title":"Nature"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.bbrc.2020.02.006","article-title":"The acetyltransferase p300 regulates NRF2 stability and localization","volume":"524","author":"Ganner","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.freeradbiomed.2010.03.017","article-title":"Triterpenoids CDDO-ethyl amide and CDDO-trifluoroethyl amide improve the behavioral phenotype and brain pathology in a transgenic mouse model of Huntington\u2019s disease","volume":"49","author":"Stack","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1038\/nchembio.1308","article-title":"Proteostasis of polyglutamine varies among neurons and predicts neurodegeneration","volume":"9","author":"Tsvetkov","year":"2013","journal-title":"Nat. Chem. Biol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.freeradbiomed.2020.03.012","article-title":"A triterpenoid Nrf2 activator, RS9, promotes LC3-associated phagocytosis of photoreceptor outer segments in a p62-independent manner","volume":"152","author":"Saito","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1083\/jcb.200507002","article-title":"p62\/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death","volume":"171","author":"Lamark","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"4584","DOI":"10.1073\/pnas.0500815102","article-title":"Extremely potent triterpenoid inducers of the phase 2 response: Correlations of protection against oxidant and inflammatory stress","volume":"102","author":"Liby","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.neuroscience.2012.07.060","article-title":"Naringin modulates oxidative stress and inflammation in 3-nitropropionic acid-induced neurodegeneration through the activation of nuclear factor-erythroid 2-related factor-2 signalling pathway","volume":"227","author":"Gopinath","year":"2012","journal-title":"Neuroscience"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/aps.2014.107","article-title":"Protopanaxtriol protects against 3-nitropropionic acid-induced oxidative stress in a rat model of Huntington\u2019s disease","volume":"36","author":"Gao","year":"2015","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.freeradbiomed.2020.10.022","article-title":"NRF2 activation by reversible KEAP1 binding induces the antioxidant response in primary neurons and astrocytes of a Huntington\u2019s disease mouse model","volume":"162","author":"Moretti","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"258","DOI":"10.3389\/fnmol.2019.00258","article-title":"The Role of Microglia and Astrocytes in Huntington\u2019s Disease","volume":"12","author":"Palpagama","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"577380","DOI":"10.1016\/j.jneuroim.2020.577380","article-title":"Inflammation in Huntington\u2019s disease: A few new twists on an old tale","volume":"348","author":"Santos","year":"2020","journal-title":"J. Neuroimmunol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1084\/jem.20080178","article-title":"A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington\u2019s disease","volume":"205","author":"Wild","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Liddell, J.R. (2017). Are Astrocytes the Predominant Cell Type for Activation of Nrf2 in Aging and Neurodegeneration?. Antioxidants, 6.","DOI":"10.3390\/antiox6030065"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1042\/BST20150014","article-title":"Dissecting molecular cross-talk between Nrf2 and NF-\u03baB response pathways","volume":"43","author":"Wardyn","year":"2015","journal-title":"Biochem. Soc. Trans."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.bcp.2007.04.008","article-title":"The anti-inflammatory actions of LCY-2-CHO, a carbazole analogue, in vascular smooth muscle cells","volume":"74","author":"Ho","year":"2007","journal-title":"Biochem. Pharmacol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"911","DOI":"10.3389\/fphar.2018.00911","article-title":"Activation of Nrf2\/HO-1 Pathway by Nardochinoid C Inhibits Inflammation and Oxidative Stress in Lipopolysaccharide-Stimulated Macrophages","volume":"9","author":"Luo","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"E4676","DOI":"10.1073\/pnas.1614943114","article-title":"KEAP1-modifying small molecule reveals muted NRF2 signaling responses in neural stem cells from Huntington\u2019s disease patients","volume":"114","author":"Quinti","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1039\/C8MD00620B","article-title":"Synthesis and discovery of asiatic acid based 1,2,3-triazole derivatives as antitumor agents blocking NF-\u03baB activation and cell migration","volume":"10","author":"Huang","year":"2019","journal-title":"Medchemcomm"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1093\/hmg\/ddx093","article-title":"TDP-43 mutations causing amyotrophic lateral sclerosis are associated with altered expression of RNA-binding protein hnRNP K and affect the Nrf2 antioxidant pathway","volume":"26","author":"Moujalled","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/nn.3584","article-title":"State of play in amyotrophic lateral sclerosis genetics","volume":"17","author":"Renton","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Obrador, E., Salvador, R., L\u00f3pez-Blanch, R., Jihad-Jebbar, A., Vall\u00e9s, S.L., and Estrela, J.M. (2020). Oxidative Stress, Neuroinflammation and Mitochondria in the Pathophysiology of Amyotrophic Lateral Sclerosis. Antioxidants, 9.","DOI":"10.3390\/antiox9090901"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1097\/NEN.0b013e31818b4906","article-title":"Nuclear erythroid 2-related factor 2-antioxidative response element signaling pathway in motor cortex and spinal cord in amyotrophic lateral sclerosis","volume":"67","author":"Sarlette","year":"2008","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0006-8993(01)02926-2","article-title":"Morphological evidence for lipid peroxidation and protein glycoxidation in spinal cords from sporadic amyotrophic lateral sclerosis patients","volume":"917","author":"Shibata","year":"2001","journal-title":"Brain Res."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1093\/hmg\/ddu578","article-title":"Phosphorylation of hnRNP K by cyclin-dependent kinase 2 controls cytosolic accumulation of TDP-43","volume":"24","author":"Moujalled","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.3892\/mmr.2014.2087","article-title":"Effect of the human SOD1-G93A gene on the Nrf2\/ARE signaling pathway in NSC-34 cells","volume":"9","author":"Wang","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"7777","DOI":"10.1523\/JNEUROSCI.0823-07.2007","article-title":"Mitochondrial superoxide production and nuclear factor erythroid 2-related factor 2 activation in p75 neurotrophin receptor-induced motor neuron apoptosis","volume":"27","author":"Pehar","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.expneurol.2007.05.026","article-title":"Activation of the Nrf2-ARE pathway in muscle and spinal cord during ALS-like pathology in mice expressing mutant SOD1","volume":"207","author":"Kraft","year":"2007","journal-title":"Exp. Neurol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3389\/fneur.2019.00068","article-title":"Diagnostic Challenge and Neuromuscular Junction Contribution to ALS Pathogenesis","volume":"10","author":"Campanari","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"5275","DOI":"10.2147\/DDDT.S281854","article-title":"Edaravone and Acetovanillone Upregulate Nrf2 and PI3K\/Akt\/mTOR Signaling and Prevent Cyclophosphamide Cardiotoxicity in Rats","volume":"14","author":"Hassanein","year":"2020","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1002\/med.21528","article-title":"Riluzole and edaravone: A tale of two amyotrophic lateral sclerosis drugs","volume":"39","author":"Jaiswal","year":"2019","journal-title":"Med. Res. Rev."},{"key":"ref_187","first-page":"467","article-title":"Edaravone attenuates traumatic brain injury through anti-inflammatory and anti-oxidative modulation","volume":"18","author":"Zhang","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.expneurol.2017.05.009","article-title":"Nrf2 activation by tauroursodeoxycholic acid in experimental models of Parkinson\u2019s disease","volume":"295","author":"Moreira","year":"2017","journal-title":"Exp. Neurol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"14941","DOI":"10.1074\/jbc.M110.211029","article-title":"Phenylbutyrate up-regulates the DJ-1 protein and protects neurons in cell culture and in animal models of Parkinson disease","volume":"286","author":"Zhou","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"15091","DOI":"10.1073\/pnas.0607260103","article-title":"DJ-1, a cancer- and Parkinson\u2019s disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2","volume":"103","author":"Clements","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.freeradbiomed.2011.03.027","article-title":"Neuroprotective effect of Nrf2\/ARE activators, CDDO ethylamide and CDDO trifluoroethylamide, in a mouse model of amyotrophic lateral sclerosis","volume":"51","author":"Neymotin","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_192","doi-asserted-by":"crossref","unstructured":"Tanaka, K., Kanno, T., Yanagisawa, Y., Yasutake, K., Inoue, S., Hirayama, N., and Ikeda, J.-E. (2014). A novel acylaminoimidazole derivative, WN1316, alleviates disease progression via suppression of glial inflammation in ALS mouse model. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087728"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1016\/j.freeradbiomed.2012.09.010","article-title":"A novel small molecule, N-(4-(2-pyridyl)(1,3-thiazol-2-yl))-2-(2,4,6-trimethylphenoxy) acetamide, selectively protects against oxidative stress-induced cell death by activating the Nrf2-ARE pathway: Therapeutic implications for ALS","volume":"53","author":"Kanno","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"13574","DOI":"10.1523\/JNEUROSCI.4099-08.2008","article-title":"Nrf2 activation in astrocytes protects against neurodegeneration in mouse models of familial amyotrophic lateral sclerosis","volume":"28","author":"Vargas","year":"2008","journal-title":"J. Neurosci"},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"Vargas, M.R., Burton, N.C., Kutzke, J., Gan, L., Johnson, D.A., Sch\u00e4fer, M., Werner, S., and Johnson, J.A. (2013). Absence of Nrf2 or its selective overexpression in neurons and muscle does not affect survival in ALS-linked mutant hSOD1 mouse models. 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