Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
NeuroMolecular Medicine
Published in: NeuroMolecular Medicine 1/2019

01-03-2019 | Alzheimer's Disease | Review Paper

Therapeutic Approaches to Alzheimer’s Disease Through Modulation of NRF2

Authors: Gahee Bahn, Dong-Gyu Jo

Published in: NeuroMolecular Medicine | Issue 1/2019

Login to get access

Abstract

The nuclear factor erythroid-derived 2-related factor 2 (NFE2L2/NRF2) is a master transcription factor that regulates oxidative stress-related genes containing the antioxidant response element (ARE) in their promoters. The damaged function and altered localization of NRF2 are found in most neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis. These neurodegenerative diseases developed from various risk factors such as accumulated oxidative stress and genetic and environmental elements. NRF2 activation protects our bodies from detrimental stress by upregulating antioxidative defense pathway, inhibiting inflammation, and maintaining protein homeostasis. NRF2 has emerged as a new therapeutic target in AD. Indeed, recent studies revealed that NRF2 activators have therapeutic effects in AD animal models and in cultured human cells that express AD pathology. This review will focus on the NRF2 pathway and the role of NRF2 in AD and suggest some NRF2 inducers as therapeutic agents for AD.
Literature
Alumkal, J. J., Slottke, R., Schwartzman, J., Cherala, G., Munar, M., Graff, J. N., et al. (2015). A phase II study of sulforaphane-rich broccoli sprout extracts in men with recurrent prostate cancer. Investigational New Drugs, 33(2), 480–489.CrossRefPubMed
Alzheimer’s Association. (2018). 2018 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia, 14(3), 367–429.CrossRef
Amin, F. U., Shah, S. A., & Kim, M. O. (2017). Vanillic acid attenuates Abeta1-42-induced oxidative stress and cognitive impairment in mice. Scientific Reports, 7, 40753.CrossRefPubMedPubMedCentral
Baek, S. H., Park, S. J., Jeong, J. I., Kim, S. H., Han, J., Kyung, J. W., et al. (2017). Inhibition of Drp1 ameliorates synaptic depression, abeta deposition, and cognitive impairment in an Alzheimer’s disease model. The Journal of Neuroscience, 37(20), 5099–5110.CrossRefPubMedPubMedCentral
Bomprezzi, R. (2015). Dimethyl fumarate in the treatment of relapsing–remitting multiple sclerosis: An overview. Therapeutic Advances in Neurological Disorders, 8(1), 20–30.CrossRefPubMedPubMedCentral
Bonda, D. J., Wang, X., Perry, G., Nunomura, A., Tabaton, M., Zhu, X., et al. (2010). Oxidative stress in Alzheimer disease: A possibility for prevention. Neuropharmacology, 59(4–5), 290–294.CrossRefPubMed
Branca, C., Ferreira, E., Nguyen, T.-V., Doyle, K., Caccamo, A., & Oddo, S. (2017). Genetic reduction of Nrf2 exacerbates cognitive deficits in a mouse model of Alzheimer’s disease. Human Molecular Genetics, 26(24), 4823–4835.CrossRefPubMedPubMedCentral
Brown, S. L., Sekhar, K. R., Rachakonda, G., Sasi, S., & Freeman, M. L. (2008). Activating transcription factor 3 is a novel repressor of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2)-regulated stress pathway. Cancer Research, 68(2), 364–368.CrossRefPubMed
Calkins, M. J., Johnson, D. A., Townsend, J. A., Vargas, M. R., Dowell, J. A., Williamson, T. P., et al. (2009). The Nrf2/ARE pathway as a potential therapeutic target in neurodegenerative disease. Antioxidants & Redox Signaling, 11(3), 497–508.CrossRef
Chang, W. H., Chen, M. C., & Cheng, I. H. (2015). Antroquinonol lowers Brain Amyloid-beta levels and improves spatial learning and memory in a transgenic mouse model of Alzheimer’s disease. Scientific Reports, 5, 15067.CrossRefPubMedPubMedCentral
Chin, M. P., Bakris, G. L., Block, G. A., Chertow, G. M., Goldsberry, A., Inker, L. A., et al. (2018). Bardoxolone methyl improves kidney function in patients with chronic kidney disease stage 4 and type 2 diabetes: Post-hoc analyses from bardoxolone methyl evaluation in patients with chronic kidney disease and type 2 diabetes study. American Journal of Nephrology, 47(1), 40–47.CrossRefPubMed
Chin, M. P., Wrolstad, D., Bakris, G. L., Chertow, G. M., de Zeeuw, D., Goldsberry, A., et al. (2014). Risk factors for heart failure in patients with type 2 diabetes mellitus and stage 4 chronic kidney disease treated with bardoxolone methyl. Journal of Cardiac Failure, 20(12), 953–958.CrossRefPubMed
Cho, D.-H., Nakamura, T., Fang, J., Cieplak, P., Godzik, A., Gu, Z., et al. (2009). S-nitrosylation of Drp1 mediates β-amyloid-related mitochondrial fission and neuronal injury. Science, 324(5923), 102–105.CrossRefPubMedPubMedCentral
Chowdhry, S., Zhang, Y., McMahon, M., Sutherland, C., Cuadrado, A., & Hayes, J. D. (2013). Nrf2 is controlled by two distinct β-TrCP recognition motifs in its Neh6 domain, one of which can be modulated by GSK-3 activity. Oncogene, 32(32), 3765.CrossRefPubMed
Cuadrado, A., Kugler, S., & Lastres-Becker, I. (2018). Pharmacological targeting of GSK-3 and NRF2 provides neuroprotection in a preclinical model of tauopathy. Redox Biology, 14, 522–534.CrossRefPubMed
Cui, Y., Ma, S., Zhang, C., Li, D., Yang, B., Lv, P., et al. (2018). Pharmacological activation of the Nrf2 pathway by 3H-1, 2-dithiole-3-thione is neuroprotective in a mouse model of Alzheimer disease. Behavioural Brain Research, 336, 219–226.CrossRefPubMed
De Zeeuw, D., Akizawa, T., Audhya, P., Bakris, G. L., Chin, M., Christ-Schmidt, H., et al. (2013). Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. New England Journal of Medicine, 369(26), 2492–2503.CrossRefPubMed
Dixit, R., Ross, J. L., Goldman, Y. E., & Holzbaur, E. L. (2008). Differential regulation of dynein and kinesin motor proteins by tau. Science, 319(5866), 1086–1089.CrossRefPubMedPubMedCentral
Dumont, M., Wille, E., Calingasan, N. Y., Tampellini, D., Williams, C., Gouras, G. K., et al. (2009). Triterpenoid CDDO-methylamide improves memory and decreases amyloid plaques in a transgenic mouse model of Alzheimer’s disease. Journal of Neurochemistry, 109(2), 502–512.CrossRefPubMedPubMedCentral
Fragoulis, A., Siegl, S., Fendt, M., Jansen, S., Soppa, U., Brandenburg, L. O., et al. (2017). Oral administration of methysticin improves cognitive deficits in a mouse model of Alzheimer’s disease. Redox Biology, 12, 843–853.CrossRefPubMedPubMedCentral
Fujiwara, K. T., Kataoka, K., & Nishizawa, M. (1993). Two new members of the maf oncogene family, mafK and mafF, encode nuclear b-Zip proteins lacking putative trans-activator domain. Oncogene, 8(9), 2371–2380.PubMed
Giraldo, E., Lloret, A., Fuchsberger, T., & Viña, J. (2014). Aβ and tau toxicities in Alzheimer’s are linked via oxidative stress-induced p38 activation: Protective role of vitamin E. Redox Biology, 2, 873–877.CrossRefPubMedPubMedCentral
Grundke-Iqbal, I., Iqbal, K., Tung, Y.-C., Quinlan, M., Wisniewski, H. M., & Binder, L. I. (1986). Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proceedings of the National Academy of Sciences USA, 83(13), 4913–4917.CrossRef
Gwon, A. R., Park, J. S., Arumugam, T. V., Kwon, Y. K., Chan, S. L., Kim, S. H., et al. (2012). Oxidative lipid modification of nicastrin enhances amyloidogenic γ-secretase activity in Alzheimer’s disease. Aging Cell, 11(4), 559–568.CrossRefPubMed
He, C. H., Gong, P., Hu, B., Stewart, D., Choi, M. E., Choi, A. M., et al. (2001). Identification of activating transcription factor 4 (ATF4) as an Nrf2-interacting protein. Implication for heme oxygenase-1 gene regulation. Journal of Biological Chemistry, 276(24), 20858–20865.CrossRefPubMed
Hinoi, E., Fujimori, S., Wang, L., Hojo, H., Uno, K., & Yoneda, Y. (2006). Nrf2 negatively regulates osteoblast differentiation via interfering with Runx2-dependent transcriptional activation. Journal of Biological Chemistry, 281(26), 18015–18024.CrossRefPubMed
Hu, C., Eggler, A. L., Mesecar, A. D., & Van Breemen, R. B. (2011). Modification of keap1 cysteine residues by sulforaphane. Chemical Research in Toxicology, 24(4), 515–521.CrossRefPubMedPubMedCentral
Itoh, K., Chiba, T., Takahashi, S., Ishii, T., Igarashi, K., Katoh, Y., et al. (1997). An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochemical and Biophysical Research Communications, 236(2), 313–322.CrossRefPubMed
Jazwa, A., Rojo, A. I., Innamorato, N. G., Hesse, M., Fernández-Ruiz, J., & Cuadrado, A. (2011). Pharmacological targeting of the transcription factor Nrf2 at the basal ganglia provides disease modifying therapy for experimental parkinsonism. Antioxidants & Redox Signaling, 14(12), 2347–2360.CrossRef
Jiao, W., Wang, Y., Kong, L., Ou-Yang, T., Meng, Q., Fu, Q., et al. (2018). CART peptide activates the Nrf2/HO-1 antioxidant pathway and protects hippocampal neurons in a rat model of Alzheimer’s disease. Biochemical and Biophysical Research Communications, 501(4), 1016–1022.CrossRefPubMed
Jing, X., Shi, H., Zhang, C., Ren, M., Han, M., Wei, X., et al. (2015). Dimethyl fumarate attenuates 6-OHDA-induced neurotoxicity in SH-SY5Y cells and in animal model of Parkinson’s disease by enhancing Nrf2 activity. Journal of Neuroscience, 286, 131–140.CrossRefPubMed
Jo, C., Gundemir, S., Pritchard, S., Jin, Y. N., Rahman, I., & Johnson, G. V. (2014). Nrf2 reduces levels of phosphorylated tau protein by inducing autophagy adaptor protein NDP52. Nature Communications, 5, 3496.CrossRefPubMed
Jo, D.-G., Arumugam, T. V., Woo, H.-N., Park, J.-S., Tang, S.-C., Mughal, M., et al. (2010). Evidence that γ-secretase mediates oxidative stress-induced β-secretase expression in Alzheimer’s disease. Neurobiology of Aging, 31(6), 917–925.CrossRefPubMed
Johnson, D. A., & Johnson, J. A. (2015). Nrf2—a therapeutic target for the treatment of neurodegenerative diseases. Free Radical Biology & Medicine, 88, 253–267.CrossRef
Joshi, G., Gan, K. A., Johnson, D. A., & Johnson, J. A. (2015). Increased Alzheimer’s disease–like pathology in the APP/PS1∆E9 mouse model lacking Nrf2 through modulation of autophagy. Neurobiology of Aging, 36(2), 664–679.CrossRefPubMed
Kanninen, K., Heikkinen, R., Malm, T., Rolova, T., Kuhmonen, S., Leinonen, H., et al. (2009). Intrahippocampal injection of a lentiviral vector expressing Nrf2 improves spatial learning in a mouse model of Alzheimer’s disease. Proceedings of the National Academy of Sciences USA, 106(38), 16505–16510.CrossRef
Kanninen, K., Malm, T. M., Jyrkkänen, H.-K., Goldsteins, G., Keksa-Goldsteine, V., Tanila, H., et al. (2008). Nuclear factor erythroid 2-related factor 2 protects against beta amyloid. Molecular Cellular Neuroscience, 39(3), 302–313.CrossRefPubMed
Karuppagounder, S. S., Xu, H., Shi, Q., Chen, L. H., Pedrini, S., Pechman, D., et al. (2009). Thiamine deficiency induces oxidative stress and exacerbates the plaque pathology in Alzheimer’s mouse model. Neurobiology of Aging, 30(10), 1587–1600.CrossRefPubMed
Katoh, Y., Itoh, K., Yoshida, E., Miyagishi, M., Fukamizu, A., & Yamamoto, M. (2001). Two domains of Nrf2 cooperatively bind CBP, a CREB binding protein, and synergistically activate transcription. Genes to Cells, 6(10), 857–868.CrossRefPubMed
Keleku-Lukwete, N., Suzuki, M., & Yamamoto, M. (2017). An overview of the advantages of KEAP1-NRF2 system activation during inflammatory disease treatment. Antioxidants & Redox Signaling, 29(17), 1746–1755.CrossRef
Kim, H. V., Kim, H. Y., Ehrlich, H. Y., Choi, S. Y., Kim, D. J., & Kim, Y. (2013a). Amelioration of Alzheimer’s disease by neuroprotective effect of sulforaphane in animal model. Amyloid, 20(1), 7–12.CrossRefPubMed
Kim, J.-H., Yu, S., Chen, J. D., & Kong, A. (2013b). The nuclear cofactor RAC3/AIB1/SRC-3 enhances Nrf2 signaling by interacting with transactivation domains. Oncogene, 32(4), 514.CrossRefPubMed
Kim, S., Choi, K. J., Cho, S. J., Yun, S. M., Jeon, J. P., Koh, Y. H., et al. (2016). Fisetin stimulates autophagic degradation of phosphorylated tau via the activation of TFEB and Nrf2 transcription factors. Scientific Reports, 6, 24933.CrossRefPubMedPubMedCentral
Kobayashi, A., Kang, M.-I., Okawa, H., Ohtsuji, M., Zenke, Y., Chiba, T., et al. (2004). Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Molecular and Cellular Biology, 24(16), 7130–7139.CrossRefPubMedPubMedCentral
Kubben, N., Zhang, W., Wang, L., Voss, T. C., Yang, J., Qu, J., et al. (2016). Repression of the antioxidant NRF2 pathway in premature aging. Cell, 165(6), 1361–1374.CrossRefPubMedPubMedCentral
Lastres-Becker, I., García-Yagüe, A. J., Scannevin, R. H., Casarejos, M. J., Kügler, S., Rábano, A., et al. (2016). Repurposing the NRF2 activator dimethyl fumarate as therapy against synucleinopathy in Parkinson’s disease. Antioxidants & Redox Signaling, 25(2), 61–77.CrossRef
Lastres-Becker, I., Innamorato, N. G., Jaworski, T., Rabano, A., Kugler, S., Van Leuven, F., et al. (2014). Fractalkine activates NRF2/NFE2L2 and heme oxygenase 1 to restrain tauopathy-induced microgliosis. Brain, 137(Pt 1), 78–91.CrossRefPubMed
Li, Z., Chen, X., Zhang, Y., Liu, X., Wang, C., Teng, L., et al. (2018). Protective roles of Amanita caesarea polysaccharides against Alzheimer’s disease via Nrf2 pathway. International Journal of Biological Macromolecules, 121, 29–37.CrossRefPubMed
Liby, K., Hock, T., Yore, M. M., Suh, N., Place, A. E., Risingsong, R., et al. (2005). The synthetic triterpenoids, CDDO and CDDO-imidazolide, are potent inducers of heme oxygenase-1 and Nrf2/ARE signaling. Cancer Research, 65(11), 4789–4798.CrossRefPubMed
Lin, M. T., & Beal, M. F. (2006). Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature, 443(7113), 787–795.CrossRefPubMed
Lindwall, G., & Cole, R. D. (1984). Phosphorylation affects the ability of tau protein to promote microtubule assembly. Journal of Biological Chemistry, 259(8), 5301–5305.PubMed
Lipton, S. A., Rezaie, T., Nutter, A., Lopez, K. M., Parker, J., Kosaka, K., et al. (2016). Therapeutic advantage of pro-electrophilic drugs to activate the Nrf2/ARE pathway in Alzheimer’s disease models. Cell Death & Disease. 7(12), e2499.CrossRef
Liu, P., Rojo de la Vega, M., Sammani, S., Mascarenhas, J. B., Kerins, M., Dodson, M., et al. (2018). RPA1 binding to NRF2 switches ARE-dependent transcriptional activation to ARE-NRE-dependent repression. Proceedings of the National Academy of Sciences USA, 115(44), e10352–e10361.CrossRef
Liu, Y., Deng, Y., Liu, H., Yin, C., Li, X., & Gong, Q. (2016). Hydrogen sulfide ameliorates learning memory impairment in APP/PS1 transgenic mice: A novel mechanism mediated by the activation of Nrf2. Pharmacology Biochemistry and Behavior, 150–151, 207–216.CrossRefPubMed
McMahon, M., Thomas, N., Itoh, K., Yamamoto, M., & Hayes, J. D. (2004). 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. Journal of Biological Chemistry, 279(30), 31556–31567.CrossRefPubMed
Moi, P., Chan, K., Asunis, I., Cao, A., & Kan, Y. W. (1994). Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proceedings of the National Academy of Sciences USA, 91(21), 9926–9930.CrossRef
Murphy, K. E., Llewellyn, K., Wakser, S., Pontasch, J., Samanich, N., Flemer, M., et al. (2018). Mini-GAGR, an intranasally applied polysaccharide, activates the neuronal Nrf2-mediated antioxidant defense system. Journal of Biological Chemistry, 293(47), 18242–18269.CrossRefPubMedPubMedCentral
Niino, M., Ohashi, T., Ochi, H., Nakashima, I., Shimizu, Y., & Matsui, M. (2018). Japanese guidelines for dimethyl fumarate. Clinical and Experimental Neuroimmunology, 9(4), 235–243.CrossRef
Nioi, P., Nguyen, T., Sherratt, P. J., & Pickett, C. B. (2005). The carboxy-terminal Neh3 domain of Nrf2 is required for transcriptional activation. Molecular and Cellular Biology, 25(24), 10895–10906.CrossRefPubMedPubMedCentral
Rada, P., Rojo, A. I., Chowdhry, S., McMahon, M., Hayes, J. D., & Cuadrado, A. (2011). SCF (beta-TrCP) promotes Glycogen synthase kinase-3-dependent degradation of the Nrf2 transcription factor in a Keap1-independent manner. Molecular and Cellular Biology, 31(6), 1121–1133.CrossRefPubMedPubMedCentral
Raina, A. K., Templeton, D. J., Deak, J. C., Perry, G., & Smith, M. A. (1999). Quinone reductase (NQO1), a sensitive redox indicator, is increased in Alzheimer’s disease. Redox Report, 4(1–2), 23–27.CrossRefPubMed
Ramsey, C. P., Glass, C. A., Montgomery, M. B., Lindl, K. A., Ritson, G. P., Chia, L. A., et al. (2007). Expression of Nrf2 in neurodegenerative diseases. Journal of Neuropathology & Experimental Neurology, 66(1), 75–85.CrossRef
René, C., Lopez, E., Claustres, M., Taulan, M., & Romey-Chatelain, M., C (2010). NF-E2-related factor 2, a key inducer of antioxidant defenses, negatively regulates the CFTR transcription. Cellular and Molecular Life Sciences, 67(13), 2297–2309.CrossRefPubMed
Rojo, A. I., Pajares, M., Rada, P., Nunez, A., Nevado-Holgado, A. J., Killik, R., et al. (2017). NRF2 deficiency replicates transcriptomic changes in Alzheimer’s patients and worsens APP and TAU pathology. Redox Biology, 13, 444–451.CrossRefPubMedPubMedCentral
Saito, R., Suzuki, T., Hiramoto, K., Asami, S., Naganuma, E., Suda, H., et al. (2016). Characterizations of three major cysteine sensors of Keap1 in stress response. Molecular and Cellular Biology, 36(2), 271–284.PubMedPubMedCentral
SantaCruz, K. S., Yazlovitskaya, E., Collins, J., Johnson, J., & DeCarli, C. (2004). Regional NAD (P) H: Quinone oxidoreductase activity in Alzheimer’s disease. Neurobiology of Aging, 25(1), 63–69.CrossRefPubMed
Sherman, M. Y., & Goldberg, A. L. (2001). Cellular defenses against unfolded proteins: A cell biologist thinks about neurodegenerative diseases. Neuron, 29(1), 15–32.CrossRefPubMed
Smith, J. A., Das, A., Ray, S. K., & Banik, N. L. (2012). Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases. Brain Research Bulletin, 87(1), 10–20.CrossRefPubMed
Suh, J. H., Shenvi, S. V., Dixon, B. M., Liu, H., Jaiswal, A. K., Liu, R.-M., et al. (2004). Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Proceedings of the National Academy of Sciences USA, 101(10), 3381–3386.CrossRef
Sun, Y., Yang, T., Mao, L., & Zhang, F. (2017). Sulforaphane protects against brain diseases: Roles of cytoprotective enzymes. Austin Journal of Cerebrovascular Disease & Stroke 4(1), 1054.
Sykiotis, G. P., & Bohmann, D. (2010). Stress-activated cap’n’collar transcription factors in aging and human disease. Science Signaling, 3(112), re3–re3.CrossRefPubMedPubMedCentral
Tanji, K., Maruyama, A., Odagiri, S., Mori, F., Itoh, K., Kakita, A., et al. (2013). Keap1 is localized in neuronal and glial cytoplasmic inclusions in various neurodegenerative diseases. Journal of Neuropathology & Experimental Neurology, 72(1), 18–28.CrossRef
Tapias, V., Jainuddin, S., Ahuja, M., Stack, C., Elipenahli, C., Vignisse, J., et al. (2018). Benfotiamine treatment activates the Nrf2/ARE pathway and is neuroprotective in a transgenic mouse model of tauopathy. Human Molecular Genetics, 27(16), 2874–2892.CrossRefPubMedPubMedCentral
Uttara, B., Singh, A. V., Zamboni, P., & Mahajan, R. (2009). Oxidative stress and neurodegenerative diseases: A review of upstream and downstream antioxidant therapeutic options. Current Neuropharmacology, 7(1), 65–74.CrossRefPubMedPubMedCentral
Venugopal, R., & Jaiswal, A. K. (1998). Nrf2 and Nrf1 in association with Jun proteins regulate antioxidant response element-mediated expression and coordinated induction of genes encoding detoxifying enzymes. Oncogene, 17(24), 3145–3156.CrossRefPubMed
Vershinin, M., Carter, B. C., Razafsky, D. S., King, S. J., & Gross, S. P. (2007). Multiple-motor based transport and its regulation by Tau. Proceedings of the National Academy of Sciences USA, 104(1), 87–92.CrossRef
Wang, C. Y., Wang, Z. Y., Xie, J. W., Wang, T., Wang, X., Xu, Y., et al. (2016). Dl-3-n-butylphthalide-induced upregulation of antioxidant defense is involved in the enhancement of cross talk between CREB and Nrf2 in an Alzheimer’s disease mouse model. Neurobiology of Aging, 38, 32–46.CrossRefPubMed
Wang, H., Liu, K., Geng, M., Gao, P., Wu, X., Hai, Y., et al. (2013). RXRα Inhibits the NRF2-ARE signalling pathway through a direct interaction With the Neh7 domain of NRF2. Cancer Research, 73(10), 3097–3108.CrossRefPubMed
Wang, L., Wang, M., Hu, J., Shen, W., Hu, J., Yao, Y., et al. (2017). Protective effect of 3H-1, 2-dithiole-3-thione on cellular model of Alzheimer’s disease involves Nrf2/ARE signaling pathway. European Journal of Pharmacology, 795, 115–123.CrossRefPubMed
Wang, W., & Jaiswal, A. K. (2006). Nuclear factor Nrf2 and antioxidant response element regulate NRH:quinone oxidoreductase 2 (NQO2) gene expression and antioxidant induction. Free Radical Biology & Medicine, 40(7), 1119–1130.CrossRef
Wang, Y., Santa-Cruz, K., DeCarli, C., & Johnson, J. A. (2000). NAD (P) H: Quinone oxidoreductase activity is increased in hippocampal pyramidal neurons of patients with Alzheimer’s disease. Neurobiology of Aging, 21(4), 525–531.CrossRefPubMed
Woo, H.-N., Park, J.-S., Gwon, A.-R., Arumugam, T. V., & Jo, D.-G. (2009). Alzheimer’s disease and notch signaling. Biochemical and Biophysical Research Communications, 390(4), 1093–1097.CrossRefPubMed
Wu, T., Zhao, F., Gao, B., Tan, C., Yagishita, N., Nakajima, T., et al. (2014). Hrd1 suppresses Nrf2-mediated cellular protection during liver cirrhosis. Genes & Development, 28(7), 708–722.CrossRef
Xie, G., Tian, W., Wei, T., & Liu, F. (2015). The neuroprotective effects of beta-hydroxybutyrate on Abeta-injected rat hippocampus in vivo and in Abeta-treated PC-12 cells in vitro. Free Radical Research, 49(2), 139–150.CrossRefPubMed
Yu, L., Wang, S., Chen, X., Yang, H., Li, X., Xu, Y., et al. (2015). Orientin alleviates cognitive deficits and oxidative stress in Abeta1-42-induced mouse model of Alzheimer’s disease. Life Sciences, 121, 104–109.CrossRefPubMed
Zhang, D. D., Lo, S.-C., Cross, J. V., Templeton, D. J., & Hannink, M. (2004). Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. Molecular and Cellular Biology, 24(24), 10941–10953.CrossRefPubMedPubMedCentral
Zhou, Y., Xie, N., Li, L., Zou, Y., Zhang, X., & Dong, M. (2014). Puerarin alleviates cognitive impairment and oxidative stress in APP/PS1 transgenic mice. International Journal of Neuropsychopharmacology, 17(4), 635–644.CrossRefPubMed
Zhu, Y. F., Li, X. H., Yuan, Z. P., Li, C. Y., Tian, R. B., Jia, W., et al. (2015). Allicin improves endoplasmic reticulum stress-related cognitive deficits via PERK/Nrf2 antioxidative signaling pathway. European Journal of Pharmacology, 762, 239–246.CrossRefPubMed
Zuo, L., Zhou, T., Pannell, B., Ziegler, A., & Best, T. M. (2015). Biological and physiological role of reactive oxygen species—the good, the bad and the ugly. Acta Physiologica, 214(3), 329–348.CrossRefPubMed
Metadata
Title
Therapeutic Approaches to Alzheimer’s Disease Through Modulation of NRF2
Authors
Gahee Bahn
Dong-Gyu Jo
Publication date
01-03-2019
Publisher
Springer US
Published in
NeuroMolecular Medicine / Issue 1/2019
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI
https://doi.org/10.1007/s12017-018-08523-5

Other articles of this Issue 1/2019

NeuroMolecular Medicine 1/2019 Go to the issue

Review Paper

The Promises and Challenges of Erythropoietin for Treatment of Alzheimer’s Disease

Original Paper

Tinospora cordifolia Suppresses Neuroinflammation in Parkinsonian Mouse Model

Original Paper

ADGRL3 rs6551665 as a Common Vulnerability Factor Underlying Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder

Original Paper

A Novel and Mosaic WDR45 Nonsense Variant Causes Beta-Propeller Protein-Associated Neurodegeneration Identified Through Whole Exome Sequencing and X chromosome Heterozygosity Analysis

Original Paper

Variants of the OLIG2 Gene are Associated with Cerebral Palsy in Chinese Han Infants with Hypoxic–Ischemic Encephalopathy

Original Paper

Hsc70 Interacts with β4GalT5 to Regulate the Growth of Gliomas