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Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Progress and Promise of Nur77-based Therapeutics for Central Nervous System Disorders

Author(s): Lu Liu, Di Ma, La Zhuo, Xinyuan Pang, Jiulin You and Jiachun Feng*

Volume 19, Issue 4, 2021

Published on: 06 June, 2020

Page: [486 - 497] Pages: 12

DOI: 10.2174/1570159X18666200606231723

Price: $65

Abstract

Nur77 belongs to the NR4A subgroup of the nuclear receptor superfamily. Unlike other nuclear receptors, a natural ligand for Nur77 has not been identified yet. However, a few small molecules can interact with this receptor and induce a conformational change to mediate its activity. The expression and activation of Nur77 can be rapidly increased using various physiological and pathological stimuli. In vivo and in vitro studies have demonstrated its regulatory role in tissues and cells of multiple systems by means of participation in cell differentiation, apoptosis, metabolism, mitochondrial homeostasis, and other processes. Although research on Nur77 in the pathophysiology of the central nervous system (CNS) is currently limited, the present data support the fact that Nur77 is involved in many neurological disorders such as stroke, multiple sclerosis, Parkinson’s disease. This indicates that activation of Nur77 has considerable potential in treating these diseases. This review summarizes the regulatory mechanisms of Nur77 in CNS diseases and presents available evidence for its potential as targeted therapy, especially for cerebrovascular and inflammationrelated CNS diseases.

Keywords: Nur77, apoptosis, inflammation, central nervous system, stroke, multiple sclerosis.

Graphical Abstract

[1]
Delgado, E.; Boisen, M.M.; Laskey, R.; Chen, R.; Song, C.; Sallit, J.; Yochum, Z.A.; Andersen, C.L.; Sikora, M.J.; Wagner, J.; Safe, S.; Elishaev, E.; Lee, A.; Edwards, R.P.; Haluska, P.; Tseng, G.; Schurdak, M.; Oesterreich, S. High expression of orphan nuclear receptor NR4A1 in a subset of ovarian tumors with worse outcome. Gynecol. Oncol., 2016, 141(2), 348-356.
[http://dx.doi.org/10.1016/j.ygyno.2016.02.030] [PMID: 26946093]
[2]
Hanna, R.N.; Shaked, I.; Hubbeling, H.G.; Punt, J.A.; Wu, R.; Herrley, E.; Zaugg, C.; Pei, H.; Geissmann, F.; Ley, K.; Hedrick, C.C. NR4A1 (Nur77) deletion polarizes macrophages toward an inflammatory phenotype and increases atherosclerosis. Circ. Res., 2012, 110(3), 416-427.
[http://dx.doi.org/10.1161/CIRCRESAHA.111.253377] [PMID: 22194622]
[3]
Saucedo-Cardenas, O.; Conneely, O.M. Comparative distribution of NURR1 and NUR77 nuclear receptors in the mouse central nervous system. J. Mol. Neurosci., 1996, 7(1), 51-53.
[http://dx.doi.org/10.1007/BF02736848]
[4]
Chang, C.; Kokontis, J.; Liao, S.S.; Chang, Y. Isolation and characterization of human TR3 receptor: a member of steroid receptor superfamily. J. Steroid Biochem., 1989, 34(1-6), 391-395.
[http://dx.doi.org/10.1016/0022-4731(89)90114-3] [PMID: 2626032]
[5]
Milbrandt, J. Nerve growth factor induces a gene homologous to the glucocorticoid receptor gene. Neuron, 1988, 1(3), 183-188.
[http://dx.doi.org/10.1016/0896-6273(88)90138-9] [PMID: 3272167]
[6]
Kumar, R.; Thompson, E.B. The structure of the nuclear hormone receptors. Steroids, 1999, 64(5), 310-319.
[http://dx.doi.org/10.1016/S0039-128X(99)00014-8] [PMID: 10406480]
[7]
Medzikovic, L.; de Vries, C.J.M.; de Waard, V. NR4A nuclear receptors in cardiac remodeling and neurohormonal regulation. Trends Cardiovasc. Med., 2018.
[PMID: 30553703]
[8]
Wu, L.; Chen, L. Characteristics of Nur77 and its ligands as potential anticancer compounds. (Review) Mol. Med. Rep., 2018, 18(6), 4793-4801.
[http://dx.doi.org/10.3892/mmr.2018.9515] [PMID: 30272297]
[9]
Lau, L.F.; Nathans, D. Expression of a set of growth-related immediate early genes in BALB/c 3T3 cells: coordinate regulation with c-fos or c-myc. Proc. Natl. Acad. Sci. USA, 1987, 84(5), 1182-1186.
[http://dx.doi.org/10.1073/pnas.84.5.1182] [PMID: 3469660]
[10]
Bing, G.Y.; Filer, D.; Miller, J.C.; Stone, E.A. Noradrenergic activation of immediate early genes in rat cerebral cortex. Brain Res. Mol. Brain Res., 1991, 11(1), 43-46.
[http://dx.doi.org/10.1016/0169-328X(91)90019-T] [PMID: 1662744]
[11]
Johansson, I.M.; Wester, P.; Háková, M.; Gu, W.; Seckl, J.R.; Olsson, T. Early and delayed induction of immediate early gene expression in a novel focal cerebral ischemia model in the rat. Eur. J. Neurosci., 2000, 12(10), 3615-3625.
[http://dx.doi.org/10.1046/j.1460-9568.2000.00252.x] [PMID: 11029632]
[12]
Kurakula, K.; Koenis, D.S.; van Tiel, C.M.; de Vries, C.J. NR4A nuclear receptors are orphans but not lonesome. Biochim. Biophys. Acta, 2014, 1843(11), 2543-2555.
[http://dx.doi.org/10.1016/j.bbamcr.2014.06.010] [PMID: 24975497]
[13]
Tomioka, T.; Maruoka, H.; Kawa, H.; Yamazoe, R.; Fujiki, D.; Shimoke, K.; Ikeuchi, T. The histone deacetylase inhibitor trichostatin A induces neurite outgrowth in PC12 cells via the epigenetically regulated expression of the nur77 gene. Neurosci. Res., 2014, 88, 39-48.
[http://dx.doi.org/10.1016/j.neures.2014.07.009] [PMID: 25128386]
[14]
Hanna, R.N.; Carlin, L.M.; Hubbeling, H.G.; Nackiewicz, D.; Green, A.M.; Punt, J.A.; Geissmann, F.; Hedrick, C.C. The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C- monocytes. Nat. Immunol., 2011, 12(8), 778-785.
[http://dx.doi.org/10.1038/ni.2063] [PMID: 21725321]
[15]
Wang, L.M.; Zhang, Y.; Li, X.; Zhang, M.L.; Zhu, L.; Zhang, G.X.; Xu, Y.M. Nr4a1 plays a crucial modulatory role in Th1/Th17 cell responses and CNS autoimmunity. Brain Behav. Immun., 2018, 68, 44-55.
[http://dx.doi.org/10.1016/j.bbi.2017.09.015] [PMID: 28962999]
[16]
Won, H.Y.; Hwang, E.S. Transcriptional modulation of regulatory T cell development by novel regulators NR4As. Arch. Pharm. Res., 2016, 39(11), 1530-1536.
[http://dx.doi.org/10.1007/s12272-016-0803-z] [PMID: 27778276]
[17]
Zhao, H.; Pan, W.; Chen, L.; Luo, Y.; Xu, R. Nur77 promotes cerebral ischemia-reperfusion injury via activating INF2-mediated mitochondrial fragmentation. J. Mol. Histol., 2018, 49(6), 599-613.
[http://dx.doi.org/10.1007/s10735-018-9798-8] [PMID: 30298449]
[18]
Xiao, G.; Sun, T.; Songming, C.; Cao, Y. NR4A1 enhances neural survival following oxygen and glucose deprivation: an in vitro study. J. Neurol. Sci., 2013, 330(1-2), 78-84.
[http://dx.doi.org/10.1016/j.jns.2013.04.010] [PMID: 23663895]
[19]
Li, H.; Kolluri, S.K.; Gu, J.; Dawson, M.I.; Cao, X.; Hobbs, P.D.; Lin, B.; Chen, G.; Lu, J.; Lin, F.; Xie, Z.; Fontana, J.A.; Reed, J.C.; Zhang, X. Cytochrome c release and apoptosis induced by mitochondrial targeting of nuclear orphan receptor TR3. Science, 2000, 289(5482), 1159-1164.
[http://dx.doi.org/10.1126/science.289.5482.1159] [PMID: 10947977]
[20]
Baxter, R.C. Insulin-like growth factor binding protein-3 (IGFBP-3): Novel ligands mediate unexpected functions. J. Cell Commun. Signal., 2013, 7(3), 179-189.
[http://dx.doi.org/10.1007/s12079-013-0203-9] [PMID: 23700234]
[21]
Li, L.; Liu, Y.; Chen, H.Z.; Li, F.W.; Wu, J.F.; Zhang, H.K.; He, J.P.; Xing, Y.Z.; Chen, Y.; Wang, W.J.; Tian, X.Y.; Li, A.Z.; Zhang, Q.; Huang, P.Q.; Han, J.; Lin, T.; Wu, Q. Impeding the interaction between Nur77 and p38 reduces LPS-induced inflammation. Nat. Chem. Biol., 2015, 11(5), 339-346.
[http://dx.doi.org/10.1038/nchembio.1788] [PMID: 25822914]
[22]
Hayden, M.S.; Ghosh, S. Signaling to NF-kappaB. Genes Dev., 2004, 18(18), 2195-2224.
[http://dx.doi.org/10.1101/gad.1228704] [PMID: 15371334]
[23]
Lin, P.C.; Chen, Y.L.; Chiu, S.C.; Yu, Y.L.; Chen, S.P.; Chien, M.H.; Chen, K.Y.; Chang, W.L.; Lin, S.Z.; Chiou, T.W.; Harn, H.J. Orphan nuclear receptor, Nurr-77 was a possible target gene of butylidenephthalide chemotherapy on glioblastoma multiform brain tumor. J. Neurochem., 2008, 106(3), 1017-1026.
[http://dx.doi.org/10.1111/j.1471-4159.2008.05432.x] [PMID: 18419761]
[24]
Chang, L.F.; Lin, P.C.; Ho, L.I.; Liu, P.Y.; Wu, W.C.; Chiang, I.P.; Chang, H.W.; Lin, S.Z.; Harn, Y.C.; Harn, H.J.; Chiou, T.W. Overexpression of the orphan receptor Nur77 and its translocation induced by PCH4 may inhibit malignant glioma cell growth and induce cell apoptosis. J. Surg. Oncol., 2011, 103(5), 442-450.
[http://dx.doi.org/10.1002/jso.21809] [PMID: 21246566]
[25]
Liang, B.; Song, X.; Liu, G.; Li, R.; Xie, J.; Xiao, L.; Du, M.; Zhang, Q.; Xu, X.; Gan, X.; Huang, D. Involvement of TR3/Nur77 translocation to the endoplasmic reticulum in ER stress-induced apoptosis. Exp. Cell Res., 2007, 313(13), 2833-2844.
[http://dx.doi.org/10.1016/j.yexcr.2007.04.032] [PMID: 17543302]
[26]
Mizushima, N.; Levine, B.; Cuervo, A.M.; Klionsky, D.J. Autophagy fights disease through cellular self-digestion. Nature, 2008, 451(7182), 1069-1075.
[http://dx.doi.org/10.1038/nature06639] [PMID: 18305538]
[27]
Hu, M.; Luo, Q.; Alitongbieke, G.; Chong, S.; Xu, C.; Xie, L.; Chen, X.; Zhang, D.; Zhou, Y.; Wang, Z.; Ye, X.; Cai, L.; Zhang, F.; Chen, H.; Jiang, F.; Fang, H.; Yang, S.; Liu, J.; Diaz-Meco, M.T.; Su, Y.; Zhou, H.; Moscat, J.; Lin, X.; Zhang, X.K. Celastrol-induced nur77 interaction with traf2 alleviates inflammation by promoting mitochondrial ubiquitination and autophagy. Mol. Cell, 2017, 66(1), 141-153.
[http://dx.doi.org/10.1016/j.molcel.2017.03.008]
[28]
Gao, H.; Chen, Z.; Fu, Y.; Yang, X.; Weng, R.; Wang, R.; Lu, J.; Pan, M.; Jin, K.; McElroy, C.; Tang, B.; Xia, Y.; Wang, Q. Nur77 exacerbates PC12 cellular injury in vitro by aggravating mitochondrial impairment and endoplasmic reticulum stress. Sci. Rep., 2016, 6, 34403.
[http://dx.doi.org/10.1038/srep34403] [PMID: 27679973]
[29]
Wang, W.J.; Wang, Y.; Chen, H.Z.; Xing, Y.Z.; Li, F.W.; Zhang, Q.; Zhou, B.; Zhang, H.K.; Zhang, J.; Bian, X.L.; Li, L.; Liu, Y.; Zhao, B.X.; Chen, Y.; Wu, R.; Li, A.Z.; Yao, L.M.; Chen, P.; Zhang, Y.; Tian, X.Y.; Beermann, F.; Wu, M.; Han, J.; Huang, P.Q.; Lin, T.; Wu, Q. Orphan nuclear receptor TR3 acts in autophagic cell death via mitochondrial signaling pathway. Nat. Chem. Biol., 2014, 10(2), 133-140.
[http://dx.doi.org/10.1038/nchembio.1406] [PMID: 24316735]
[30]
Bouzas-Rodríguez, J.; Zárraga-Granados, G. Sánchez-Carbente, Mdel.R.; Rodríguez-Valentín, R.; Gracida, X.; Anell-Rendón, D.; Covarrubias, L.; Castro-Obregón, S. The nuclear receptor NR4A1 induces a form of cell death dependent on autophagy in mammalian cells. PLoS One, 2012, 7(10), e46422.
[http://dx.doi.org/10.1371/journal.pone.0046422] [PMID: 23071566]
[31]
Liebmann, M.; Hucke, S.; Koch, K.; Eschborn, M.; Ghelman, J.; Chasan, A.I.; Glander, S.; Schädlich, M.; Kuhlencord, M.; Daber, N.M.; Eveslage, M.; Beyer, M.; Dietrich, M.; Albrecht, P.; Stoll, M.; Busch, K.B.; Wiendl, H.; Roth, J.; Kuhlmann, T.; Klotz, L. Nur77 serves as a molecular brake of the metabolic switch during T cell activation to restrict autoimmunity. Proc. Natl. Acad. Sci. USA, 2018, 115(34), E8017-E8026.
[http://dx.doi.org/10.1073/pnas.1721049115] [PMID: 30072431]
[32]
Stadelmann, C.; Wegner, C.; Brück, W. Inflammation, demyelination, and degeneration - recent insights from MS pathology. Biochim. Biophys. Acta, 2011, 1812(2), 275-282.
[http://dx.doi.org/10.1016/j.bbadis.2010.07.007] [PMID: 20637864]
[33]
Croxford, A.L.; Kurschus, F.C.; Waisman, A. Mouse models for multiple sclerosis: historical facts and future implications. Biochim. Biophys. Acta, 2011, 1812(2), 177-183.
[http://dx.doi.org/10.1016/j.bbadis.2010.06.010] [PMID: 20600870]
[34]
Achiron, A.; Grotto, I.; Balicer, R.; Magalashvili, D.; Feldman, A.; Gurevich, M. Microarray analysis identifies altered regulation of nuclear receptor family members in the pre-disease state of multiple sclerosis. Neurobiol. Dis., 2010, 38(2), 201-209.
[http://dx.doi.org/10.1016/j.nbd.2009.12.029] [PMID: 20079437]
[35]
Achiron, A.; Feldman, A.; Gurevich, M. Characterization of multiple sclerosis traits: nuclear receptors (NR) impaired apoptosis pathway and the role of 1-α 25-dihydroxyvitamin D3. J. Neurol. Sci., 2011, 311(1-2), 9-14.
[http://dx.doi.org/10.1016/j.jns.2011.06.038] [PMID: 21752397]
[36]
Lee, I.H.; Finkel, T. Metabolic regulation of the cell cycle. Curr. Opin. Cell Biol., 2013, 25(6), 724-729.
[http://dx.doi.org/10.1016/j.ceb.2013.07.002] [PMID: 23890700]
[37]
Araujo, L.P.; Maricato, J.T.; Guereschi, M.G.; Takenaka, M.C.; Nascimento, V.M.; de Melo, F.M.; Quintana, F.J.; Brum, P.C.; Basso, A.S. The Sympathetic Nervous System Mitigates CNS Autoimmunity via β2-Adrenergic Receptor Signaling in Immune Cells. Cell Rep., 2019, 28(12), 3120-3130.e5.
[http://dx.doi.org/10.1016/j.celrep.2019.08.042] [PMID: 31533035]
[38]
Vujnović, I.; Pilipović, I.; Jasnić, N.; Petrović, R.; Blagojević, V.; Arsenović-Ranin, N.; Stojić-Vukanić, Z.; Djordjević, J.; Leposavić, G. Noradrenaline through β-adrenoceptor contributes to sexual dimorphism in primary CD4+ T-cell response in DA rat EAE model? Cell. Immunol., 2019, 336, 48-57.
[http://dx.doi.org/10.1016/j.cellimm.2018.12.009] [PMID: 30600100]
[39]
Shaked, I.; Hanna, R.N.; Shaked, H.; Chodaczek, G.; Nowyhed, H.N.; Tweet, G.; Tacke, R.; Basat, A.B.; Mikulski, Z.; Togher, S.; Miller, J.; Blatchley, A.; Salek-Ardakani, S.; Darvas, M.; Kaikkonen, M.U.; Thomas, G.D.; Lai-Wing-Sun, S.; Rezk, A.; Bar-Or, A.; Glass, C.K.; Bandukwala, H.; Hedrick, C.C. Transcription factor Nr4a1 couples sympathetic and inflammatory cues in CNS-recruited macrophages to limit neuroinflammation. Nat. Immunol., 2015, 16(12), 1228-1234.
[http://dx.doi.org/10.1038/ni.3321] [PMID: 26523867]
[40]
Brendecke, S.M.; Prinz, M. Do not judge a cell by its cover--diversity of CNS resident, adjoining and infiltrating myeloid cells in inflammation. Semin. Immunopathol., 2015, 37(6), 591-605.
[http://dx.doi.org/10.1007/s00281-015-0520-6] [PMID: 26251238]
[41]
Zrzavy, T.; Hametner, S.; Wimmer, I.; Butovsky, O.; Weiner, H.L.; Lassmann, H. Loss of ‘homeostatic’ microglia and patterns of their activation in active multiple sclerosis. Brain, 2017, 140(7), 1900-1913.
[http://dx.doi.org/10.1093/brain/awx113] [PMID: 28541408]
[42]
Parkhurst, C.N.; Yang, G.; Ninan, I.; Savas, J.N.; Yates, J.R., III; Lafaille, J.J.; Hempstead, B.L.; Littman, D.R.; Gan, W-B. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell, 2013, 155(7), 1596-1609.
[http://dx.doi.org/10.1016/j.cell.2013.11.030] [PMID: 24360280]
[43]
Yamasaki, R.; Lu, H.; Butovsky, O.; Ohno, N.; Rietsch, A.M.; Cialic, R.; Wu, P.M.; Doykan, C.E.; Lin, J.; Cotleur, A.C.; Kidd, G.; Zorlu, M.M.; Sun, N.; Hu, W.; Liu, L.; Lee, J-C.; Taylor, S.E.; Uehlein, L.; Dixon, D.; Gu, J.; Floruta, C.M.; Zhu, M.; Charo, I.F.; Weiner, H.L.; Ransohoff, R.M. Differential roles of microglia and monocytes in the inflamed central nervous system. J. Exp. Med., 2014, 211(8), 1533-1549.
[http://dx.doi.org/10.1084/jem.20132477] [PMID: 25002752]
[44]
Rothe, T.; Ipseiz, N.; Faas, M.; Lang, S.; Perez-Branguli, F.; Metzger, D.; Ichinose, H.; Winner, B.; Schett, G.; Krönke, G. The nuclear receptor nr4a1 acts as a microglia rheostat and serves as a therapeutic target in autoimmune-driven central nervous system inflammation. J. Immunol., 2017, 198(10), 3878-3885.
[http://dx.doi.org/10.4049/jimmunol.1600638] [PMID: 28411187]
[45]
Bonta, P.I.; Matlung, H.L.; Vos, M.; Peters, S.L.M.; Pannekoek, H.; Bakker, E.N.T.P.; de Vries, C.J.M. Nuclear receptor Nur77 inhibits vascular outward remodelling and reduces macrophage accumulation and matrix metalloproteinase levels. Cardiovasc. Res., 2010, 87(3), 561-568.
[http://dx.doi.org/10.1093/cvr/cvq064] [PMID: 20189954]
[46]
Glagov, S.; Weisenberg, E.; Zarins, C.K.; Stankunavicius, R.; Kolettis, G.J. Compensatory enlargement of human atherosclerotic coronary arteries. N. Engl. J. Med., 1987, 316(22), 1371-1375.
[http://dx.doi.org/10.1056/NEJM198705283162204] [PMID: 3574413]
[47]
Schoenhagen, P.; Ziada, K.M.; Kapadia, S.R.; Crowe, T.D.; Nissen, S.E.; Tuzcu, E.M. Extent and direction of arterial remodeling in stable versus unstable coronary syndromes: an intravascular ultrasound study. Circulation, 2000, 101(6), 598-603.
[http://dx.doi.org/10.1161/01.CIR.101.6.598] [PMID: 10673250]
[48]
Yang, P.; Wei, X.; Zhang, J.; Yi, B.; Zhang, G-X.; Yin, L.; Yang, X-F.; Sun, J. Antithrombotic effects of nur77 and nor1 are mediated through upregulating thrombomodulin expression in endothelial cells. Arterioscler. Thromb. Vasc. Biol., 2016, 36(2), 361-369.
[http://dx.doi.org/10.1161/ATVBAHA.115.306891] [PMID: 26634653]
[49]
Dai, Y.; Sun, Q.; Zhang, X.; Hu, Y.; Zhou, M.; Shi, J. Cyclosporin A ameliorates early brain injury after subarachnoid hemorrhage through inhibition of a Nur77 dependent apoptosis pathway. Brain Res., 2014, 1556, 67-76.
[http://dx.doi.org/10.1016/j.brainres.2014.01.052] [PMID: 24508908]
[50]
Dai, Y.; Zhang, W.; Sun, Q.; Zhang, X.; Zhou, X.; Hu, Y.; Shi, J. Nuclear receptor nur77 promotes cerebral cell apoptosis and induces early brain injury after experimental subarachnoid hemorrhage in rats. J. Neurosci. Res., 2014, 92(9), 1110-1121.
[http://dx.doi.org/10.1002/jnr.23392] [PMID: 24737679]
[51]
Li, R.; Xin, T.; Li, D.; Wang, C.; Zhu, H.; Zhou, H. Therapeutic effect of Sirtuin 3 on ameliorating nonalcoholic fatty liver disease: The role of the ERK-CREB pathway and Bnip3-mediated mitophagy. Redox Biol., 2018, 18, 229-243.
[http://dx.doi.org/10.1016/j.redox.2018.07.011] [PMID: 30056271]
[52]
Gan, L.; Wang, Z.; Si, J.; Zhou, R.; Sun, C.; Liu, Y.; Ye, Y.; Zhang, Y.; Liu, Z.; Zhang, H. Protective effect of mitochondrial-targeted antioxidant MitoQ against iron ion 56Fe radiation induced brain injury in mice. Toxicol. Appl. Pharmacol., 2018, 341, 1-7.
[http://dx.doi.org/10.1016/j.taap.2018.01.003] [PMID: 29317239]
[53]
Zhang, Y.J.; Song, J.R.; Zhao, M.J. NR4A1 regulates cerebral ischemia-induced brain injury by regulating neuroinflammation through interaction with NF-κB/p65. Biochem. Biophys. Res. Commun., 2019, 518(1), 59-65.
[http://dx.doi.org/10.1016/j.bbrc.2019.08.008] [PMID: 31445702]
[54]
Boche, D.; Donald, J.; Love, S.; Harris, S.; Neal, J.W.; Holmes, C.; Nicoll, J.A.R. Reduction of aggregated Tau in neuronal processes but not in the cell bodies after Abeta42 immunisation in Alzheimer’s disease. Acta Neuropathol., 2010, 120(1), 13-20.
[http://dx.doi.org/10.1007/s00401-010-0705-y] [PMID: 20532897]
[55]
Hawk, J.D.; Bookout, A.L.; Poplawski, S.G.; Bridi, M.; Rao, A.J.; Sulewski, M.E.; Kroener, B.T.; Manglesdorf, D.J.; Abel, T. NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors. J. Clin. Invest., 2012, 122(10), 3593-3602.
[http://dx.doi.org/10.1172/JCI64145] [PMID: 22996661]
[56]
Dickey, C.A.; Loring, J.F.; Montgomery, J.; Gordon, M.N.; Eastman, P.S.; Morgan, D. Selectively reduced expression of synaptic plasticity-related genes in amyloid precursor protein + presenilin-1 transgenic mice. J. Neurosci., 2003, 23(12), 5219-5226.
[http://dx.doi.org/10.1523/JNEUROSCI.23-12-05219.2003] [PMID: 12832546]
[57]
Dickey, C.A.; Gordon, M.N.; Mason, J.E.; Wilson, N.J.; Diamond, D.M.; Guzowski, J.F.; Morgan, D. Amyloid suppresses induction of genes critical for memory consolidation in APP + PS1 transgenic mice. J. Neurochem., 2004, 88(2), 434-442.
[http://dx.doi.org/10.1111/j.1471-4159.2004.02185.x] [PMID: 14690531]
[58]
Montarolo, F.; Perga, S.; Martire, S.; Navone, D.N.; Marchet, A.; Leotta, D.; Bertolotto, A. Altered NR4A subfamily gene expression level in peripheral blood of Parkinson’s and Alzheimer’s Disease Patients. Neurotox. Res., 2016, 30(3), 338-344.
[http://dx.doi.org/10.1007/s12640-016-9626-4] [PMID: 27159982]
[59]
Newman, S.J.; Bond, B.; Crook, B.; Darker, J.; Edge, C.; Maycox, P.R. Neuron-specific localisation of the TR3 death receptor in Alzheimer’s disease. Brain Res., 2000, 857(1-2), 131-140.
[http://dx.doi.org/10.1016/S0006-8993(99)02417-8] [PMID: 10700560]
[60]
Zhao, Y.; Liu, Y.; Zheng, D. Alpha 1-antichymotrypsin/SerpinA3 is a novel target of orphan nuclear receptor Nur77. FEBS J., 2008, 275(5), 1025-1038.
[http://dx.doi.org/10.1111/j.1742-4658.2008.06269.x] [PMID: 18248459]
[61]
Liu, Y.; Tang, J.; Gao, X.; Wang, M.; Shen, J.; You, X. Effect of retinoid X receptor-α nuclear export inhibition on apoptosis of neurons in vivo and in vitro. Mol. Med. Rep., 2017, 16(2), 2037-2044.
[http://dx.doi.org/10.3892/mmr.2017.6766] [PMID: 28627642]
[62]
Bezard, E.; Brotchie, J.M.; Gross, C.E. Pathophysiology of levodopa-induced dyskinesia: potential for new therapies. Nat. Rev. Neurosci., 2001, 2(8), 577-588.
[http://dx.doi.org/10.1038/35086062] [PMID: 11484001]
[63]
St-Hilaire, M.; Landry, E.; Lévesque, D.; Rouillard, C. Denervation and repeated L-DOPA induce a coordinate expression of the transcription factor NGFI-B in striatal projection pathways in hemi-parkinsonian rats. Neurobiol. Dis., 2003, 14(1), 98-109.
[http://dx.doi.org/10.1016/S0969-9961(03)00081-0] [PMID: 13678671]
[64]
Sgambato-Faure, V.; Buggia, V.; Gilbert, F.; Lévesque, D.; Benabid, A-L.; Berger, F. Coordinated and spatial upregulation of arc in striatonigral neurons correlates with L-dopa-induced behavioral sensitization in dyskinetic rats. J. Neuropathol. Exp. Neurol., 2005, 64(11), 936-947.
[http://dx.doi.org/10.1097/01.jnen.0000186922.42592.b7] [PMID: 16254488]
[65]
Mahmoudi, S.; Samadi, P.; Gilbert, F.; Ouattara, B.; Morissette, M.; Grégoire, L.; Rouillard, C.; Di Paolo, T.; Lévesque, D. Nur77 mRNA levels and L-Dopa-induced dyskinesias in MPTP monkeys treated with docosahexaenoic acid. Neurobiol. Dis., 2009, 36(1), 213-222.
[http://dx.doi.org/10.1016/j.nbd.2009.07.017] [PMID: 19635563]
[66]
Mount, M.P.; Zhang, Y.; Amini, M.; Callaghan, S.; Kulczycki, J.; Mao, Z.; Slack, R.S.; Anisman, H.; Park, D.S. Perturbation of transcription factor Nur77 expression mediated by myocyte enhancer factor 2D (MEF2D) regulates dopaminergic neuron loss in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). J. Biol. Chem., 2013, 288(20), 14362-14371.
[http://dx.doi.org/10.1074/jbc.M112.439216] [PMID: 23536182]
[67]
Rouillard, C.; Baillargeon, J.; Paquet, B.; St-Hilaire, M.; Maheux, J.; Lévesque, C.; Darlix, N.; Majeur, S.; Lévesque, D. Genetic disruption of the nuclear receptor Nur77 (Nr4a1) in rat reduces dopamine cell loss and l-Dopa-induced dyskinesia in experimental Parkinson’s disease. Exp. Neurol., 2018, 304, 143-153.
[http://dx.doi.org/10.1016/j.expneurol.2018.03.008] [PMID: 29530712]
[68]
Pekny, M.; Wilhelmsson, U.; Pekna, M. The dual role of astrocyte activation and reactive gliosis. Neurosci. Lett., 2014, 565, 30-38.
[http://dx.doi.org/10.1016/j.neulet.2013.12.071] [PMID: 24406153]
[69]
Popichak, K.A.; Hammond, S.L.; Moreno, J.A.; Afzali, M.F.; Backos, D.S.; Slayden, R.D.; Safe, S.; Tjalkens, R.B. Compensatory Expression of Nur77 and Nurr1 Regulates NF-κB-Dependent Inflammatory Signaling in Astrocytes. Mol. Pharmacol., 2018, 94(4), 1174-1186.
[http://dx.doi.org/10.1124/mol.118.112631] [PMID: 30111648]
[70]
Liu, T.Y.; Yang, X.Y.; Zheng, L.T.; Wang, G.H.; Zhen, X.C. Activation of Nur77 in microglia attenuates proinflammatory mediators production and protects dopaminergic neurons from inflammation-induced cell death. J. Neurochem., 2017, 140(4), 589-604.
[http://dx.doi.org/10.1111/jnc.13907] [PMID: 27889907]
[71]
No, H.; Bang, Y.; Lim, J.; Kim, S.S.; Choi, H.S.; Choi, H.J. Involvement of induction and mitochondrial targeting of orphan nuclear receptor Nur77 in 6-OHDA-induced SH-SY5Y cell death. Neurochem. Int., 2010, 56(4), 620-626.
[http://dx.doi.org/10.1016/j.neuint.2010.01.005] [PMID: 20096738]
[72]
Wei, X.; Gao, H.; Zou, J.; Liu, X.; Chen, D.; Liao, J.; Xu, Y.; Ma, L.; Tang, B.; Zhang, Z.; Cai, X.; Jin, K.; Xia, Y.; Wang, Q. Contra-directional coupling of Nur77 and Nurr1 in neurodegeneration: a novel mechanism for memantine-induced anti-inflammation and anti-mitochondrial impairment. Mol. Neurobiol., 2016, 53(9), 5876-5892.
[http://dx.doi.org/10.1007/s12035-015-9477-7] [PMID: 26497037]
[73]
Mathisen, G.H.; Fallgren, A.B.; Strøm, B.O.; Boldingh, D.K.A.; Mohebi, B.U.; Paulsen, R.E. Delayed translocation of NGFI-B/RXR in glutamate stimulated neurons allows late protection by 9-cis retinoic acid. Biochem. Biophys. Res. Commun., 2011, 414(1), 90-95.
[http://dx.doi.org/10.1016/j.bbrc.2011.09.028] [PMID: 21945431]
[74]
Huang, H.M.; Yu, J.Y.; Ou, H.C.; Jeng, K.C. Effect of naloxone on the induction of immediately early genes following oxygen- and glucose-deprivation in PC12 cells. Neurosci. Lett., 2008, 438(2), 252-256.
[http://dx.doi.org/10.1016/j.neulet.2008.04.036] [PMID: 18457920]
[75]
Dai, Y.; Zhang, W.; Zhou, X.; Shi, J. Inhibition of c-Jun N-terminal kinase ameliorates early brain injury after subarachnoid hemorrhage through inhibition of a Nur77 dependent apoptosis pathway. Neurochem. Res., 2014, 39(8), 1603-1611.
[http://dx.doi.org/10.1007/s11064-014-1355-6] [PMID: 24928238]
[76]
Dai, Y.; Jin, W.; Cheng, L.; Yu, C.; Chen, C.; Ni, H. Nur77 is a promoting factor in traumatic brain injury-induced nerve cell apoptosis. Biomed. Pharmacother., 2018, 108, 774-782.
[http://dx.doi.org/10.1016/j.biopha.2018.09.091]
[77]
Zhang, W.; Zhu, X.; Liu, Y.; Chen, M.; Yan, S.; Mao, X.; Liu, Z.; Wu, W.; Chen, C.; Xu, X.; Wang, Y. Nur77 was essential for neurite outgrowth and involved in schwann cell differentiation after sciatic nerve injury. J. Mol. Neurosci., 2015, 57(1), 38-47.
[http://dx.doi.org/10.1007/s12031-015-0575-9]
[78]
Huang, H.Y.; Chang, H.F.; Tsai, M.J.; Chen, J.S.; Wang, M.J. 6-Mercaptopurine attenuates tumor necrosis factor-α production in microglia through Nur77-mediated transrepression and PI3K/Akt/mTOR signaling-mediated translational regulation. J. Neuroinflammation, 2016, 13(1), 78.
[http://dx.doi.org/10.1186/s12974-016-0543-5] [PMID: 27075886]

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