Role of Nrf2 in neurotoxicity of environmental electrophiles

Abdalla MY, Ahmad IM, Switzer B, Britigan BE (2015) Induction of heme oxygenase-1 contributes to survival of Mycobacterium abscessus in human macrophages-like THP-1 cells. Redox Biol 4:328-39 doi:10.1016/j.redox.2015.01.012

Ahmed SM, Luo L, Namani A, Wang XJ, Tang X (2017) Nrf2 signaling pathway: Pivotal roles in inflammation. Biochim Biophys Acta Mol Basis Dis 1863(2):585-597 doi:10.1016/j.bbadis.2016.11.005

Ahn YH, Hwang Y, Liu H, et al. (2010) Electrophilic tuning of the chemoprotective natural product sulforaphane. Proc Natl Acad Sci U S A 107(21):9590-5 doi:10.1073/pnas.1004104107

Akiyama M, Unoki T, Shinkai Y, et al. (2019) Environmental Electrophile-Mediated Toxicity in Mice Lacking Nrf2, CSE, or Both. Environ Health Perspect 127(6):67002 doi:10.1289/EHP4949

Angeloni C, Leoncini E, Malaguti M, Angelini S, Hrelia P, Hrelia S (2009) Modulation of phase II enzymes by sulforaphane: implications for its cardioprotective potential. J Agric Food Chem 57(12):5615-22 doi:10.1021/jf900549c

Auld RB, Bedwell SF (1967) Peripheral neuropathy with sympathetic overactivity from industrial contact with acrylamide. Can Med Assoc J 96(11):652-4

Baek SH, Park M, Suh JH, Choi HS (2008) Protective effects of an extract of young radish (Raphanus sativus L) cultivated with sulfur (sulfur-radish extract) and of sulforaphane on carbon tetrachloride-induced hepatotoxicity. Biosci Biotechnol Biochem 72(5):1176-82 doi:10.1271/bbb.70545

Bailey SL, Carpentier PA, McMahon EJ, Begolka WS, Miller SD (2006) Innate and adaptive immune responses of the central nervous system. Crit Rev Immunol 26(2):149-88 doi:doi: 10.1615/critrevimmunol.v26.i2.40

Baird L, Dinkova-Kostova AT (2011) The cytoprotective role of the Keap1-Nrf2 pathway. Arch Toxicol 85(4):241-72 doi:10.1007/s00204-011-0674-5

Baird L, Swift S, Lleres D, Dinkova-Kostova AT (2014) Monitoring Keap1-Nrf2 interactions in single live cells. Biotechnol Adv 32(6):1133-44 doi:10.1016/j.biotechadv.2014.03.004

Bazan NG, Halabi A, Ertel M, Petasis NA (2012) Chapter 34 - Neuroinflammation. In: Brady ST, Siegel GJ, Albers RW, Price DL (eds) Basic Neurochemistry (Eighth Edition). Academic Press, New York, p 610-620

Bellezza I, Tucci A, Galli F, et al. (2012) Inhibition of NF-κB nuclear translocation via HO-1 activation underlies α-tocopheryl succinate toxicity. J Nutr Biochem 23(12):1583-91 doi:10.1016/j.jnutbio.2011.10.012

Belzung C, El Hage W, Moindrot N, Griebel G (2001) Behavioral and neurochemical changes following predatory stress in mice. Neuropharmacology 41(3):400-8 doi:doi: 10.1016/s0028- 3908(01)00072-7

Berendse HW, Galis-de Graaf Y, Groenewegen HJ (1992) Topographical organization and relationship with ventral striatal compartments of prefrontal corticostriatal projections in the rat. J Comp Neurol 316(3):314-47 doi:10.1002/cne.903160305

Bergmark E (1997) Hemoglobin adducts of acrylamide and acrylonitrile in laboratory workers, smokers and nonsmokers. Chem Res Toxicol 10(1):78-84 doi:doi: 10.1021/tx960113p

Bicks LK, Koike H, Akbarian S, Morishita H (2015) Prefrontal Cortex and Social Cognition in Mouse and Man. Front Psychol 6:1805 doi:10.3389/fpsyg.2015.01805

Block ML, Zecca L, Hong JS (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8(1):57-69 doi:10.1038/nrn2038

Bradley WG, Asbury AK (1970) Radioautographic studies of Schwann cell behavior. I. Acrylamide neuropathy in the mouse. J Neuropathol Exp Neurol 29(3):500-6 doi:10.1097/00005072- 197007000-00011

Brandenburg LO, Kipp M, Lucius R, Pufe T, Wruck CJ (2010) Sulforaphane suppresses LPS- induced inflammation in primary rat microglia. Inflamm Res 59(6):443-50 doi:10.1007/s00011-009-0116-5

Brigelius-Flohé R, Flohé L (2011) Basic principles and emerging concepts in the redox control of transcription factors. Antioxid Redox Signal 15(8):2335-81 doi:10.1089/ars.2010.3534

Brunetti D, Bottani E, Segala A, et al. (2020) Targeting Multiple Mitochondrial Processes by a Metabolic Modulator Prevents Sarcopenia and Cognitive Decline in SAMP8 Mice. Front Pharmacol 11:1171 doi:10.3389/fphar.2020.01171

Bufalari I, Aprile T, Avenanti A, Di Russo F, Aglioti SM (2007) Empathy for pain and touch in the human somatosensory cortex. Cereb Cortex 17(11):2553-61 doi:10.1093/cercor/bhl161

Cabe PA, Colwell PB (1981) Toxic effects of acrylamide in Japanese quail (Coturnix coturnix Japonica). J Toxicol Environ Health 7(6):935-40 doi:10.1080/15287398109530036

Calleman CJ (1996) The metabolism and pharmacokinetics of acrylamide: implications for mechanisms of toxicity and human risk estimation. Drug Metab Rev 28(4):527-90 doi:10.3109/03602539608994018

Cardona AE, Pioro EP, Sasse ME, et al. (2006) Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci 9(7):917-24 doi:10.1038/nn1715

Cavins JF, Friedman M (1968) Specific modification of protein sulfhydryl groups with alpha,beta- unsaturated compounds. J Biol Chem 243(12):3357-60

Cenquizca LA, Swanson LW (2007) Spatial organization of direct hippocampal field CA1 axonal projections to the rest of the cerebral cortex. Brain Res Rev 56(1):1-26 doi:10.1016/j.brainresrev.2007.05.002

Chanas SA, Jiang Q, McMahon M, et al. (2002) 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. Biochem J 365(Pt 2):405-16 doi:10.1042/BJ20020320

Checker R, Patwardhan RS, Sharma D, et al. (2012) Schisandrin B exhibits anti-inflammatory activity through modulation of the redox-sensitive transcription factors Nrf2 and NF-κB. Free Radic Biol Med 53(7):1421-30 doi:10.1016/j.freeradbiomed.2012.08.006

Chiang SK, Chen SE, Chang LC (2018) A Dual Role of Heme Oxygenase-1 in Cancer Cells. Int J Mol Sci 20(1) doi:10.3390/ijms20010039

Chorley BN, Campbell MR, Wang X, et al. (2012) Identification of novel NRF2-regulated genes by ChIP-Seq: influence on retinoid X receptor alpha. Nucleic Acids Res 40(15):7416-29 doi:10.1093/nar/gks409

Chung C, Kim T, Kim M, et al. (2013) Hippo-Foxa2 signaling pathway plays a role in peripheral lung maturation and surfactant homeostasis. Proc Natl Acad Sci U S A 110(19):7732-7 doi:10.1073/pnas.1220603110

Clark J, Simon DK (2009) Transcribe to survive: transcriptional control of antioxidant defense programs for neuroprotection in Parkinson's disease. Antioxid Redox Signal 11(3):509-28 doi:10.1089/ars.2008.2241

Cornblatt BS, Ye L, Dinkova-Kostova AT, et al. (2007) Preclinical and clinical evaluation of sulforaphane for chemoprevention in the breast. Carcinogenesis 28(7):1485-90 doi:10.1093/carcin/bgm049

Croxson PL, Johansen-Berg H, Behrens TE, et al. (2005) Quantitative investigation of connections of the prefrontal cortex in the human and macaque using probabilistic diffusion tractography. J Neurosci 25(39):8854-66 doi:10.1523/jneurosci.1311-05.2005

Damasio AR (1995) On some functions of the human prefrontal cortex. Ann N Y Acad Sci 769:241- 51 doi:10.1111/j.1749-6632.1995.tb38142.x

Dayalan Naidu S, Dinkova-Kostova AT (2020) KEAP1, a cysteine-based sensor and a drug target for the prevention and treatment of chronic disease. Open Biol 10(6):200105 doi:10.1098/rsob.200105

De La Garza R, Asnis GM (2003) The non-steroidal anti-inflammatory drug diclofenac sodium attenuates IFN-α induced alterations to monoamine turnover in prefrontal cortex and hippocampus. Brain Res 977(1):70-79 doi:10.1016/s0006-8993(03)02757-4

Dearfield KL, Abernathy CO, Ottley MS, Brantner JH, Hayes PF (1988) Acrylamide: its metabolism, developmental and reproductive effects, genotoxicity, and carcinogenicity. Mutat Res 195(1):45-77 doi:10.1016/0165-1110(88)90015-2

Dearfield KL, Douglas GR, Ehling UH, Moore MM, Sega GA, Brusick DJ (1995) Acrylamide: a review of its genotoxicity and an assessment of heritable genetic risk. Mutat Res 330(1-2):71- 99 doi:10.1016/0027-5107(95)00037-j

Deng H, He F, Zhang S, Calleman CJ, Costa LG (1993) Quantitative measurements of vibration threshold in healthy adults and acrylamide workers. Int Arch Occup Environ Health 65(1):53- 6 doi:10.1007/bf00586059

Denzer I, Münch G, Pischetsrieder M, Friedland K (2016) S-allyl-L-cysteine and isoliquiritigenin improve mitochondrial function in cellular models of oxidative and nitrosative stress. Food Chem 194:843-8 doi:10.1016/j.foodchem.2015.08.052

Dinkova-Kostova AT, Holtzclaw WD, Cole RN, et al. (2002) Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proc Natl Acad Sci U S A 99(18):11908-13 doi:10.1073/pnas.172398899

Dinkova-Kostova AT, Talalay P (2008) Direct and indirect antioxidant properties of inducers of cytoprotective proteins. Mol Nutr Food Res 52 Suppl 1:S128-38 doi:10.1002/mnfr.200700195

Drees D, Crago F, Hopper C, Smith J (1976) Subchronic percutaneous toxicity of acrylamide and methylacrylamide in the new-born rabbit. Toxicol Appl Pharmacol 37: A234 190 Duffy S, So A, Murphy TH (1998) Activation of endogenous antioxidant defenses in neuronal cells

prevents free radical-mediated damage. J Neurochem 71(1):69-77 doi:10.1046/j.1471- 4159.1998.71010069.x

Duncan J, Owen AM (2000) Common regions of the human frontal lobe recruited by diverse cognitive demands. Trends Neurosci 23(10):475-83 doi:10.1016/s0166-2236(00)01633-7

Dunn AJ, Wang J, Ando T (1999) Effects of Cytokines on Cerebral Neurotransmission Adv Exp Med Biol. Springer US, p 117-127

Edwards PM (1975) Neurotoxicity of acrylamide and its analogues and effects of these analogues and other agents on acrylamide neuropathy. Br J Ind Med 32(1):31-8 doi:10.1136/oem.32.1.31

Edwards PM, Parker VH (1977) A simple, sensitive, and objective method for early assessment of acrylamide neuropathy in rats. Toxicol Appl Pharmacol 40(3):589-591 doi:10.1016/0041- 008x(77)90083-7

Eickhoff SB, Jbabdi S, Caspers S, et al. (2010) Anatomical and functional connectivity of cytoarchitectonic areas within the human parietal operculum. J Neurosci 30(18):6409-21 doi:10.1523/jneurosci.5664-09.2010

Ekuban FA, Zong C, Takikawa M, et al. (2021a) Genetic ablation of Nrf2 exacerbates neurotoxic effects of acrylamide in mice. Toxicology 456:152785 doi:https://doi.org/10.1016/j.tox.2021.152785

Ekuban FA, Zong C, Takikawa M, et al. (2021b) Genetic ablation of Nrf2 exacerbates neurotoxic effects of acrylamide in mice. Toxicology:152785 doi:https://doi.org/10.1016/j.tox.2021.152785

Elbert T, Candia V, Altenmüller E, et al. (1998) Alteration of digital representations in somatosensory cortex in focal hand dystonia. Neuroreport 9(16):3571-5 doi:10.1097/00001756-199811160-00006

Elmore JS, Koutsidis G, Dodson AT, Mottram DS, Wedzicha BL (2005) The effect of cooking on acrylamide and its precursors in potato, wheat and rye. Adv Exp Med Biol 561:255-69 doi:10.1007/0-387-24980-x_19

Endresen L, Bakka A, Rugstad HE (1983) Increased resistance to chlorambucil in cultured cells with a high concentration of cytoplasmic metallothionein. Cancer Res 43(6):2918-26

Erkekoğlu P, Baydar T (2010) Toxicity of acrylamide and evaluation of its exposure in baby foods. Nutr Res Rev 23(2):323-33 doi:10.1017/s0954422410000211

Eskin TA, Lapham LW, Maurissen JP, Merigan WH (1985) Acrylamide effects on the macaque visual system. II. Retinogeniculate morphology. Invest Ophthalmol Vis Sci 26(3):317-29

European Food Safety Agency EFSA (2015) EFSA Panel on Contaminants in the Food Chain (CONTAM), Scientific Opinion on acrylamide in food EFSA Journal. vol 13. Wiley

Exon JH (2006) A review of the toxicology of acrylamide. J Toxicol Environ Health B Crit Rev 9(5):397-412 doi:10.1080/10937400600681430

Folkard DL, Melchini A, Traka MH, et al. (2014) Suppression of LPS-induced transcription and cytokine secretion by the dietary isothiocyanate sulforaphane. Mol Nutr Food Res 58(12):2286-96 doi:10.1002/mnfr.201400550

Franklin KBJ, Chudasama Y (2012) Prefrontal Cortex The Mouse Nervous System. Elsevier, p 727- 735

Friedman M (2003) Chemistry, Biochemistry, and Safety of Acrylamide. A Review. J Agric Food Chem 51(16):4504-26 doi:10.1021/jf030204+

Friedman MA, Dulak LH, Stedham MA (1995) A Lifetime Oncogenicity Study in Rats with Acrylamide. Toxicol Sci 27(1):95-105 doi:10.1093/toxsci/27.1.95

Fullerton PM, Barnes JM (1966) Peripheral neuropathy in rats produced by acrylamide. Br J Ind Med 23(3):210-21 doi:10.1136/oem.23.3.210

Gaona-Gaona L, Molina-Jijón E, Tapia E, et al. (2011) Protective effect of sulforaphane pretreatment against cisplatin-induced liver and mitochondrial oxidant damage in rats. Toxicology 286(1- 3):20-7 doi:10.1016/j.tox.2011.04.014

Garland TO, Patterson MW (1967a) Six cases of acrylamide poisoning. Br Med J 4(5572):134-8 doi:10.1136/bmj.4.5572.134

Garland TO, Patterson MW (1967b) Six cases of acrylamide poisoning. BMJ 4(5572):134-138 doi:10.1136/bmj.4.5572.134

Gehrmann J, Matsumoto Y, Kreutzberg GW (1995) Microglia: Intrinsic immuneffector cell of the brain. Brain Res Rev 20(3):269-287 doi:10.1016/0165-0173(94)00015-h

Ghorbel I, Elwej A, Chaabene M, et al. (2017) Effects of acrylamide graded doses on metallothioneins I and II induction and DNA fragmentation: Bochemical and histomorphological changes in the liver of adult rats. Toxicol Ind Health 33(8):611-622 doi:10.1177/0748233717696613

Gilbert SG, Maurissen JPJ (1982) Assessment of the effects of acrylamide, methylmercury, and 2,5‐ hexanedione on motor functions in mice. J Toxicol Environ Health 10(1):31-41 doi:10.1080/15287398209530228

Grudzien A, Shaw P, Weintraub S, Bigio E, Mash DC, Mesulam MM (2007) Locus coeruleus neurofibrillary degeneration in aging, mild cognitive impairment and early Alzheimer's disease. Neurobiol Aging 28(3):327-335 doi:10.1016/j.neurobiolaging.2006.02.007

Gu J, Cheng Y, Wu H, et al. (2017) Metallothionein Is Downstream of Nrf2 and Partially Mediates Sulforaphane Prevention of Diabetic Cardiomyopathy. Diabetes 66(2):529-542 doi:10.2337/db15-1274

Gu X, Manautou JE (2012) Molecular mechanisms underlying chemical liver injury. Expert Rev Mol Med 14:e4 doi:10.1017/s1462399411002110

Gunawan B, Kaplowitz N (2004) Clinical perspectives on xenobiotic-induced hepatotoxicity. Drug Metab Rev 36(2):301-12 doi:10.1081/dmr-120034148

Hanisch U-K (2002) Microglia as a source and target of cytokines. Glia 40(2):140-155 doi:10.1002/glia.10161

Hanna DE, Solomon CT, Poste AE, Buck DG, Chapman LJ (2015) A review of mercury concentrations in freshwater fishes of Africa: patterns and predictors. Environ Toxicol Chem 34(2):215-23 doi:10.1002/etc.2818

Hao Q, Maret W (2006) Aldehydes release zinc from proteins. A pathway from oxidative stress/lipid peroxidation to cellular functions of zinc. FEBS J 273(18):4300-10 doi:10.1111/j.1742- 4658.2006.05428.x

Hashimoto K, Sakamoto J, Tanii H (1981) Neurotoxicity of acrylamide and related compounds and their effects on male gonads in mice. Arch Toxicol 47(3):179-89 doi:10.1007/bf00368678

Hayashi A, Suzuki H, Itoh K, Yamamoto M, Sugiyama Y (2003) Transcription factor Nrf2 is required for the constitutive and inducible expression of multidrug resistance-associated protein1 in mouse embryo fibroblasts. Biochem Biophys Res Commun 310(3):824-829 doi:10.1016/j.bbrc.2003.09.086

Hayes JD, Dinkova-Kostova AT (2014) The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem Sci 39(4):199-218 doi:10.1016/j.tibs.2014.02.002

Heiss E, Herhaus C, Klimo K, Bartsch H, Gerhäuser C (2001) Nuclear factor kappa B is a molecular target for sulforaphane-mediated anti-inflammatory mechanisms. J Biol Chem 276(34):32008-15 doi:10.1074/jbc.M104794200

Hirotsu Y, Katsuoka F, Funayama R, et al. (2012) Nrf2–MafG heterodimers contribute globally to antioxidant and metabolic networks. Nucleic Acids Res 40(20):10228-10239 doi:10.1093/nar/gks827

Hirsch EC, Hunot S (2009) Neuroinflammation in Parkinson's disease: a target for neuroprotection? Lancet Neurol 8(4):382-97 doi:10.1016/s1474-4422(09)70062-6

Hiser J, Koenigs M (2018) The Multifaceted Role of the Ventromedial Prefrontal Cortex in Emotion, Decision Making, Social Cognition, and Psychopathology. Biol Psychiatry 83(8):638-647 doi:10.1016/j.biopsych.2017.10.030

Hong F, Freeman ML, Liebler DC (2005) Identification of sensor cysteines in human Keap1 modified by the cancer chemopreventive agent sulforaphane. Chem Res Toxicol 18(12):1917-26 doi:10.1021/tx0502138

Hopkins A (1970) The effect of acrylamide on the peripheral nervous system of the baboon. J Neurol Neurosurg Psychiatry 33(6):805-16 doi:10.1136/jnnp.33.6.805

Hopkins AP, Gilliatt RW (1971) Motor and sensory nerve conduction velocity in the baboon: normal values and changes during acrylamide neuropathy. J Neurol Neurosurg Psychiatry 34(4):415- 26 doi:10.1136/jnnp.34.4.415

Hu X, Leak RK, Shi Y, et al. (2015) Microglial and macrophage polarization—new prospects for brain repair. Nat Rev Neurol 11(1):56-64 doi:10.1038/nrneurol.2014.207

Hughes E, Newton D, Harling R, Begg S (1994) Validation of neurotoxicity screen with reference to motor and locomotor functions., Huntingdon Cambridgeshire: Huntingdon Research Centre. Ltd.

Hummelsheim H, Bianchetti M, Wiesendanger M, Wiesendanger R (1988) Sensory inputs to the agranular motor fields: a comparison between precentral, supplementary-motor and premotor areas in the monkey. Exp Brain Res 69(2):289-98 doi:10.1007/bf00247574

IARC (1994) Monographs on the evaluation of carcinogenic risks to human: some industrial chemicals. International Agency for Research on Cancer, Lyon, France, p pp. 389–433

Igisu H, Goto I, Kawamura Y, Kato M, Izumi K (1975) Acrylamide encephaloneuropathy due to well water pollution. J Neurol Neurosurg Psychiatry 38(6):581-584 doi:10.1136/jnnp.38.6.581

Innamorato NG, Jazwa A, Rojo AI, et al. (2010) Different Susceptibility to the Parkinson's Toxin MPTP in Mice Lacking the Redox Master Regulator Nrf2 or Its Target Gene Heme Oxygenase-1. PLoS One 5(7):e11838 doi:10.1371/journal.pone.0011838

Innamorato NG, Rojo AI, García-Yagüe AJ, Yamamoto M, de Ceballos ML, Cuadrado A (2008) The transcription factor Nrf2 is a therapeutic target against brain inflammation. J Immunol 181(1):680-9 doi:10.4049/jimmunol.181.1.680

Ishihara K, Matsunaga A, Miyoshi T, et al. (2005) Formation of acrylamide in a processed food model system, and examination of inhibitory conditions. Shokuhin Eiseigaku Zasshi 46(2):33-9 doi:10.3358/shokueishi.46.33

Ishii Y, Itoh K, Morishima Y, et al. (2005) Transcription Factor Nrf2 Plays a Pivotal Role in Protection against Elastase-Induced Pulmonary Inflammation and Emphysema. The Journal of Immunology 175(10):6968-6975 doi:doi: 10.4049/jimmunol.175.10.6968

Ishikawa J, Ishikawa A, Nakamura S (2007) Interferon-alpha reduces the density of monoaminergic axons in the rat brain. Neuroreport 18(2):137-140 doi:10.1097/wnr.0b013e328010231a

Itoh K, Chiba T, Takahashi S, et al. (1997) An Nrf2/Small Maf Heterodimer Mediates the Induction of Phase II Detoxifying Enzyme Genes through Antioxidant Response Elements. Biochem Biophys Res Commun 236(2):313-322 doi:10.1006/bbrc.1997.6943

Itoh K, Mochizuki M, Ishii Y, et al. (2004) Transcription Factor Nrf2 Regulates Inflammation by Mediating the Effect of 15-Deoxy-Δ12,14-Prostaglandin J2. Mol Cell Biol 24(1):36-45 doi:10.1128/mcb.24.1.36-45.2004

Itoh K, Wakabayashi N, Katoh Y, Ishii T, O'Connor T, Yamamoto M (2003) Keap1 regulates both cytoplasmic-nuclear shuttling and degradation of Nrf2 in response to electrophiles. Genes Cells 8(4):379-391 doi:10.1046/j.1365-2443.2003.00640.x

Izumi Y, Kataoka H, Inose Y, Akaike A, Koyama Y, Kume T (2018) Neuroprotective effect of an Nrf2-ARE activator identified from a chemical library on dopaminergic neurons. Eur J Pharmacol 818:470-479 doi:10.1016/j.ejphar.2017.11.023

Jacobs M, Premji A, Nelson AJ (2012) Plasticity-inducing TMS protocols to investigate somatosensory control of hand function. Neural Plast 2012:350574 doi:10.1155/2012/350574

Jan AT, Azam M, Siddiqui K, Ali A, Choi I, Haq QM (2015) Heavy Metals and Human Health: Mechanistic Insight into Toxicity and Counter Defense System of Antioxidants. Int J Mol Sci 16(12):29592-630 doi:10.3390/ijms161226183

Jazwa A, Rojo AI, Innamorato NG, 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. Antioxid Redox Signal 14(12):2347-60 doi:10.1089/ars.2010.3731

Jiang YM, Wang Y, Tan HS, et al. (2016) Schisandrol B protects against acetaminophen-induced acute hepatotoxicity in mice via activation of the NRF2/ARE signaling pathway. Acta pharmacologica Sinica 37(3):382-9 doi:10.1038/aps.2015.120

Jiao Y, Sun Z, Lee T, et al. (1999) A simple and sensitive antigen retrieval method for free-floating and slide-mounted tissue sections. J Neurosci Methods 93(2):149-162 doi:10.1016/s0165- 0270(99)00142-9

Johnson JA, Johnson DA, Kraft AD, et al. (2008) The Nrf2-ARE pathway: an indicator and modulator of oxidative stress in neurodegeneration. Ann N Y Acad Sci 1147:61-9 doi:10.1196/annals.1427.036

Johnson K (1986) Chronic toxicity and oncogenicity study on acrylamide incorporated in the drinking water of Fischer 344 rats. Toxicol Appl Pharmacol 85(2):154-168 doi:10.1016/0041-008x(86)90109-2

Juge N, Mithen RF, Traka M (2007) Molecular basis for chemoprevention by sulforaphane: a comprehensive review. Cell Mol Life Sci 64(9):1105-27 doi:10.1007/s00018-007-6484-5

Kaas JH, Nelson RJ, Sur M, Lin CS, Merzenich MM (1979) Multiple representations of the body within the primary somatosensory cortex of primates. Science 204(4392):521-3 doi:10.1126/science.107591

Kema IP, de Vries EG, Muskiet FA (2000) Clinical chemistry of serotonin and metabolites. J Chromatogr B Biomed Sci Appl 747(1-2):33-48 doi:10.1016/s0378-4347(00)00341-8

Kesson CM, Baird AW, Lawson DH (1977) Acrylamide poisoning. Postgrad Med J 53(615):16-17 doi:10.1136/pgmj.53.615.16

Kim J, Cha Y-N, Surh Y-J (2010) A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 690(1-2):12-23 doi:10.1016/j.mrfmmm.2009.09.007

Kim JH, Nam YP, Jeon SM, Han HS, Suk K (2012) Amyloid neurotoxicity is attenuated by metallothionein: dual mechanisms at work. J Neurochem 121(5):751-62 doi:10.1111/j.1471- 4159.2012.07725.x

Kobayashi A, Kang M-I, Okawa H, et al. (2004) Oxidative Stress Sensor Keap1 Functions as an Adaptor for Cul3-Based E3 Ligase To Regulate Proteasomal Degradation of Nrf2. Mol Cell Biol 24(16):7130-7139 doi:10.1128/mcb.24.16.7130-7139.2004

Kobayashi E, Suzuki T, Yamamoto M (2013) Roles Nrf2 Plays in Myeloid Cells and Related Disorders. Oxid Med Cell Longev 2013:1-7 doi:10.1155/2013/529219

Kobayashi EH, Suzuki T, Funayama R, et al. (2016) Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription. Nat Commun 7:11624 doi:10.1038/ncomms11624

Komada M, Hara N, Kawachi S, et al. (2017) Mechanisms underlying neuro-inflammation and neurodevelopmental toxicity in the mouse neocortex following prenatal exposure to ethanol. Sci Rep 7(1):4934 doi:10.1038/s41598-017-04289-1

Konczak J, Abbruzzese G (2013) Focal dystonia in musicians: linking motor symptoms to somatosensory dysfunction. Front Hum Neurosci 7:297 doi:10.3389/fnhum.2013.00297

Kraft AD, Harry GJ (2011) Features of microglia and neuroinflammation relevant to environmental exposure and neurotoxicity. Int J Environ Res Public Health 8(7):2980-3018 doi:10.3390/ijerph8072980

Kropf E, Syan SK, Minuzzi L, Frey BN (2019) From anatomy to function: the role of the somatosensory cortex in emotional regulation. Braz J Psychiatry 41(3):261-269 doi:10.1590/1516-4446-2018-0183

Kumagai Y, Abiko Y (2017) Environmental Electrophiles: Protein Adducts, Modulation of Redox Signaling, and Interaction with Persulfides/Polysulfides. Chem Res Toxicol 30(1):203-219 doi:10.1021/acs.chemrestox.6b00326

Kuperman AS (1958) Effects of acrylamide on the central nervous system of the cat. J Pharmacol Exp Ther 123(3):180-92

Kwak M-K, Wakabayashi N, Itoh K, Motohashi H, Yamamoto M, Kensler TW (2002) Modulation of Gene Expression by Cancer Chemopreventive Dithiolethiones through the Keap1-Nrf2 Pathway. J Biol Chem 278(10):8135-8145 doi:10.1074/jbc.m211898200

Lalonde R, Strazielle C (2011) Brain regions and genes affecting limb-clasping responses. Brain Res Rev 67(1-2):252-9 doi:10.1016/j.brainresrev.2011.02.005

Lawson LJ, Perry VH, Dri P, Gordon S (1990) Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience 39(1):151-170 doi:10.1016/0306- 4522(90)90229-w

Lee DF, Kuo HP, Liu M, et al. (2009) KEAP1 E3 ligase-mediated downregulation of NF-kappaB signaling by targeting IKKbeta. Mol Cell 36(1):131-40 doi:10.1016/j.molcel.2009.07.025

Leswing RJ, Ribelin WE (1969) Physiologic and pathologic changes in acrylamide neuropathy. Arch Environ Health 18(1):23-9

Levonen A-L, Landar A, Ramachandran A, et al. (2004) Cellular mechanisms of redox cell signalling: role of cysteine modification in controlling antioxidant defences in response to electrophilic lipid oxidation products. Biochem J 378(2):373-382 doi:10.1042/bj20031049

Li H, Luo N, Li YW, et al. (2017) Cadmium in rice: Transport mechanisms, influencing factors, and minimizing measures. Environ Pollut 224:622-630 doi:10.1016/j.envpol.2017.01.087

Li J, Lee JM, Johnson JA (2002) Microarray analysis reveals an antioxidant responsive element- driven gene set involved in conferring protection from an oxidative stress-induced apoptosis in IMR-32 cells. J Biol Chem 277(1):388-94 doi:10.1074/jbc.M109380200

Lin W, Wu RT, Wu T, Khor TO, Wang H, Kong AN (2008) Sulforaphane suppressed LPS-induced inflammation in mouse peritoneal macrophages through Nrf2 dependent pathway. Biochem Pharmacol 76(8):967-73 doi:10.1016/j.bcp.2008.07.036

Liu F, Ichihara S, Valentine WM, et al. (2010) Increased Susceptibility of Nrf2-Null Mice to 1- Bromopropane–Induced Hepatotoxicity. Toxicol Sci 115(2):596-606 doi:10.1093/toxsci/kfq075

Liu Y, Nakamura S (2006) Stress-induced plasticity of monoamine axons. Front Biosci 11(1):1794- 1801 doi:10.2741/1923

LoPachin RM (2004) The Changing View of Acrylamide Neurotoxicity. Neurotoxicology 25(4):617- 630 doi:doi: 10.1016/j.neuro.2004.01.004

LoPachin RM, Barber DS (2006) Synaptic cysteine sulfhydryl groups as targets of electrophilic neurotoxicants. Toxicol Sci 94(2):240-55 doi:10.1093/toxsci/kfl066

Lopachin RM, Barber DS, Geohagen BC, Gavin T, He D, Das S (2007) Structure-toxicity analysis of type-2 alkenes: in vitro neurotoxicity. Toxicol Sci 95(1):136-46 doi:10.1093/toxsci/kfl127

LoPachin RM, Gavin T (2008) Acrylamide-Induced Nerve Terminal Damage: Relevance to Neurotoxic and Neurodegenerative Mechanisms. J Agric Food Chem 56(15):5994-6003 doi:10.1021/jf703745t

LoPachin RM, Gavin T (2012) Molecular Mechanism of Acrylamide Neurotoxicity: Lessons Learned from Organic Chemistry. Environ Health Perspect 120(12):1650-1657 doi:10.1289/ehp.1205432

LoPachin RM, Gavin T (2016) Reactions of electrophiles with nucleophilic thiolate sites: relevance to pathophysiological mechanisms and remediation. Free Radic Res 50(2):195-205 doi:doi: 10.3109/10715762.2015.1094184

Lopachin RM, Gavin T, Decaprio A, Barber DS (2012) Application of the Hard and Soft, Acids and Bases (HSAB) theory to toxicant--target interactions. Chem Res Toxicol 25(2):239-51 doi:10.1021/tx2003257

LoPachin RM, Ross JF, Lehning EJ (2002a) Nerve Terminals as the Primary Site of Acrylamide Action: A Hypothesis. Neurotoxicology 23(1):43-59 doi:10.1016/s0161-813x(01)00074-2

LoPachin RM, Ross JF, Reid ML, Das S, Mansukhani S, Lehning EJ (2002b) Neurological Evaluation of Toxic Axonopathies in Rats: Acrylamide and 2,5-Hexanedione. Neurotoxicology 23(1):95-110 doi:10.1016/s0161-813x(02)00003-7

Lövheim H (2012) A new three-dimensional model for emotions and monoamine neurotransmitters. Med Hypotheses 78(2):341-348 doi:10.1016/j.mehy.2011.11.016

Lowndes HE, Baker T, Cho ES, Jortner BS (1978) Position sensitivity of de-efferented muscle spindles in experimental acrylamide neuropathy. J Pharmacol Exp Ther 205(1):40-8

Lu Y, Zhang Y, Lou Y, Cui W, Miao L (2020) Sulforaphane suppresses obesity-related glomerulopathy-induced damage by enhancing autophagy via Nrf2. Life Sci 258:118153 doi:10.1016/j.lfs.2020.118153

Lukac H, Amrein TM, Perren R, Conde-Petit B, Amadò R, Escher F (2007) Influence of roasting conditions on the acrylamide content and the color of roasted almonds. J Food Sci 72(1):C033-8 doi:10.1111/j.1750-3841.2006.00206.x

MacLeod AK, McMahon M, Plummer SM, et al. (2009) Characterization of the cancer chemopreventive NRF2-dependent gene battery in human keratinocytes: demonstration that the KEAP1–NRF2 pathway, and not the BACH1–NRF2 pathway, controls cytoprotection against electrophiles as well as redox-cycling compounds. Carcinogenesis 30(9):1571-1580 doi:10.1093/carcin/bgp176

Maher JM, Dieter MZ, Aleksunes LM, et al. (2007) Oxidative and electrophilic stress induces multidrug resistance-associated protein transporters via the nuclear factor-E2-related factor-2 transcriptional pathway. Hepatology 46(5):1597-1610 doi:10.1002/hep.21831

Mangiarini L, Sathasivam K, Seller M, et al. (1996) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87(3):493-506 doi:10.1016/s0092-8674(00)81369-0

Marcyniuk B, Mann DMA, Yates PO (1986) Loss of nerve cells from locus coeruleus in Alzheimer's disease is topographically arranged. Neurosci Lett 64(3):247-252 doi:10.1016/0304- 3940(86)90336-8

Maret W (2003) Cellular zinc and redox states converge in the metallothionein/thionein pair. J Nutr 133(5 Suppl 1):1460s-2s doi:10.1093/jn/133.5.1460S

Maret W (2011) Redox biochemistry of mammalian metallothioneins. J Biol Inorg Chem 16(7):1079-86 doi:10.1007/s00775-011-0800-0

Mas S, Gassó P, Trias G, Bernardo M, Lafuente A (2012) Sulforaphane protects SK-N-SH cells against antipsychotic-induced oxidative stress. Fundam Clin Pharmacol 26(6):712-21 doi:10.1111/j.1472-8206.2011.00988.x

McCollister DD, Oyen F, Rowe VK (1964) TOXICOLOGY OF ACRYLAMIDE. Ther Ggw 103:172-81 doi:10.1016/0041-008x(64)90103-6

McMahon M, Itoh K, Yamamoto M, Hayes JD (2003) Keap1-dependent Proteasomal Degradation of Transcription Factor Nrf2 Contributes to the Negative Regulation of Antioxidant Response Element-driven Gene Expression. J Biol Chem 278(24):21592-21600 doi:10.1074/jbc.m300931200

McMahon M, Lamont DJ, Beattie KA, Hayes JD (2010) Keap1 perceives stress via three sensors for the endogenous signaling molecules nitric oxide, zinc, and alkenals. Proc Natl Acad Sci U S A 107(44):18838-43 doi:10.1073/pnas.1007387107

Mezzaroma E, Toldo S, Farkas D, et al. (2011) The inflammasome promotes adverse cardiac remodeling following acute myocardial infarction in the mouse. Proc Natl Acad Sci U S A 108(49):19725-30 doi:10.1073/pnas.1108586108

Miller MS, Spencer PS (1985) The mechanisms of acrylamide axonopathy. Annu Rev Pharmacol Toxicol 25:643-66 doi:10.1146/annurev.pa.25.040185.003235

Miura T, Shinkai Y, Jiang H-Y, et al. (2011) Initial Response and Cellular Protection Through the Keap1/Nrf2 System During the Exposure of Primary Mouse Hepatocytes to 1,2- naphthoquinone. Chem Res Toxicol 24(4):559-67 doi:10.1021/tx100427p

Mizuno K, Kume T, Muto C, et al. (2011) Glutathione biosynthesis via activation of the nuclear factor E2-related factor 2 (Nrf2)--antioxidant-response element (ARE) pathway is essential for neuroprotective effects of sulforaphane and 6-(methylsulfinyl) hexyl isothiocyanate. J Pharmacol Sci 115(3):320-8 doi:10.1254/jphs.10257fp

Mojska H, Gielecińska I, Cendrowski A (2016) Acrylamide content in cigarette mainstream smoke and estimation of exposure to acrylamide from tobacco smoke in Poland. Ann Agric Environ Med 23(3):456-61 doi:10.5604/12321966.1219187

Morimoto M (1975) Occurence of human cases intoxicated with well water contaminated with acrylamide in fukuoka prfecture. Water waste 17:51-62

Morroni F, Tarozzi A, Sita G, et al. (2013) Neuroprotective effect of sulforaphane in 6- hydroxydopamine-lesioned mouse model of Parkinson's disease. Neurotoxicology 36:63-71 doi:10.1016/j.neuro.2013.03.004

Motohashi H, O'Connor T, Katsuoka F, Engel JD, Yamamoto M (2002) Integration and diversity of the regulatory network composed of Maf and CNC families of transcription factors. Gene 294(1-2):1-12 doi:10.1016/s0378-1119(02)00788-6

Motohashi H, Yamamoto M (2004) Nrf2–Keap1 defines a physiologically important stress response mechanism. Trends Mol Med 10(11):549-557 doi:10.1016/j.molmed.2004.09.003

Mottram DS, Wedzicha BL, Dodson AT (2002) Acrylamide is formed in the Maillard reaction. Nature 419(6906):448-449 doi:10.1038/419448a

Mundorf ML, Joseph JD, Austin CM, Caron MG, Wightman RM (2001) Catecholamine release and uptake in the mouse prefrontal cortex. J Neurochem 79(1):130-42 doi:10.1046/j.1471- 4159.2001.00554.x

Murphy TH, De Long MJ, Coyle JT (1991) Enhanced NAD(P)H:quinone reductase activity prevents glutamate toxicity produced by oxidative stress. J Neurochem 56(3):990-5 doi:10.1111/j.1471-4159.1991.tb02019.x

Nagashima D, Zhang L, Kitamura Y, et al. (2019) Proteomic analysis of hippocampal proteins in acrylamide-exposed Wistar rats. Arch Toxicol 93(7):1993-2006 doi:10.1007/s00204-019- 02484-9

Newton D, Hughes E, Harling R, Gopinath C, Beg S (1992) A neurotoxicity screen in rats following treatment with acrylamide, carbaryl or p,p’-DDT., vol As cited by JECFA (2006). , Huntingdon, Cambridgeshire: Huntingdon Research Centre Ltd.

Nitti M, Piras S, Marinari UM, Moretta L, Pronzato MA, Furfaro AL (2017) HO-1 Induction in Cancer Progression: A Matter of Cell Adaptation. Antioxidants (Basel) 6(2) doi:10.3390/antiox6020029

Ogura T, Tong KI, Mio K, et al. (2010a) Keap1 is a forked-stem dimer structure with two large spheres enclosing the intervening, double glycine repeat, and C-terminal domains.

Proceedings of the National Academy of Sciences 107(7):2842-2847 doi:10.1073/pnas.0914036107

Ogura T, Tong KI, Mio K, et al. (2010b) Keap1 is a forked-stem dimer structure with two large spheres enclosing the intervening, double glycine repeat, and C-terminal domains. Proc Natl Acad Sci U S A 107(7):2842-7 doi:10.1073/pnas.0914036107

Oh SH, Deagen JT, Whanger PD, Weswig PH (1978) Biological function of metallothionein. V. Its induction in rats by various stresses. Am J Physiol 234(3):E282-5 doi:10.1152/ajpendo.1978.234.3.E282

Ongür D, Price JL (2000) The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cereb Cortex 10(3):206-19 doi:10.1093/cercor/10.3.206

Paxinos G, Franklin KBJ (2004) The Mouse Brain in Stereotaxic Coordinates, 2 edn. Elsevier Academic Press, United States of America

Pepe G, Calderazzi G, De Maglie M, Villa AM, Vegeto E (2014) Heterogeneous induction of microglia M2a phenotype by central administration of interleukin-4. J Neuroinflammation 11:211 doi:10.1186/s12974-014-0211-6

Petering DH, Krezoski S, Tabatabai NM (2009) 12 Metallothionein Toxicology: Metal Ion Trafficking and Cellular Protection Metallothioneins and Related Chelators. In: Sigel H, Sigel A, Sigel RKO (eds) Metallothioneins and Related Chelators. vol 48. De Gruyter, p 353-398

Prawan A, Kundu JK, Surh YJ (2005) Molecular basis of heme oxygenase-1 induction: implications for chemoprevention and chemoprotection. Antioxid Redox Signal 7(11-12):1688-703 doi:10.1089/ars.2005.7.1688

Ressler KJ, Nemeroff CB (1999) Role of norepinephrine in the pathophysiology and treatment of mood disorders. Biol Psychiatry 46(9):1219-1233 doi:10.1016/s0006-3223(99)00127-4

Rho HJ, Kim JH, Lee SH (2018) Function of Selective Neuromodulatory Projections in the Mammalian Cerebral Cortex: Comparison Between Cholinergic and Noradrenergic Systems. Front Neural Circuits 12:47 doi:10.3389/fncir.2018.00047

Rice JM (2005) The carcinogenicity of acrylamide. Mutat Res 580(1-2):3-20 doi:10.1016/j.mrgentox.2004.09.008

Rojo AI, Innamorato NG, Martín-Moreno AM, De Ceballos ML, Yamamoto M, Cuadrado A (2009) Nrf2 regulates microglial dynamics and neuroinflammation in experimental Parkinson's disease. Glia 58(5):588-598 doi:10.1002/glia.20947

Ruenz M, Bakuradze T, Eisenbrand G, Richling E (2016) Monitoring urinary mercapturic acids as biomarkers of human dietary exposure to acrylamide in combination with acrylamide uptake assessment based on duplicate diets. Arch Toxicol 90(4):873-81 doi:10.1007/s00204-015- 1494-9

Saika F, Matsuzaki S, Kobayashi D, Kiguchi N, Kishioka S (2018) Chemokine CXCL1 is responsible for cocaine-induced reward in mice. Neuropsychopharmacol Rep 38(3):145-148 doi:10.1002/npr2.12018

Satchell PM, McLeod JG (1981) Megaoesophagus due to acrylamide neuropathy. J Neurol Neurosurg Psychiatry 44(10):906-13 doi:10.1136/jnnp.44.10.906

Saxena PR (1995) Serotonin receptors: Subtypes, functional responses and therapeutic relevance. Pharmacol Ther 66(2):339-368 doi:10.1016/0163-7258(94)00005-n

Schepici G, Bramanti P, Mazzon E (2020) Efficacy of Sulforaphane in Neurodegenerative Diseases. Int J Mol Sci 21(22) doi:10.3390/ijms21228637

Schilling M, Besselmann M, Leonhard C, Mueller M, Ringelstein EB, Kiefer R (2003) Microglial activation precedes and predominates over macrophage infiltration in transient focal cerebral ischemia: a study in green fluorescent protein transgenic bone marrow chimeric mice. Exp Neurol 183(1):25-33 doi:10.1016/s0014-4886(03)00082-7

Schneider CA, Rasband WS, Eliceiri KW (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9(7):671-5 doi:10.1038/nmeth.2089

Sega GA, Alcota RP, Tancongco CP, Brimer PA (1989) Acrylamide binding to the DNA and protamine of spermiogenic stages in the mouse and its relationship to genetic damage. Mutat Res 216(4):221-30 doi:10.1016/0165-1161(89)90008-3

Segerbäck D, Calleman CJ, Schroeder JL, Costa LG, Faustman EM (1995) Formation of N-7-(2- carbamoyl-2-hydroxyethyl)guanine in DNA of the mouse and the rat following intraperitoneal administration of [14C]acrylamide. Carcinogenesis 16(5):1161-5 doi:10.1093/carcin/16.5.1161

Sehsah R, Wu W, Ichihara S, et al. (2019) Role of Nrf2 in inflammatory response in lung of mice exposed to zinc oxide nanoparticles. Part Fibre Toxicol 16(1) doi:10.1186/s12989-019-0328- y

Shanmugam G, Narasimhan M, Tamowski S, Darley-Usmar V, Rajasekaran NS (2017) Constitutive activation of Nrf2 induces a stable reductive state in the mouse myocardium. Redox biology 12:937-945 doi:10.1016/j.redox.2017.04.038

Shinkai Y, Kimura T, Itagaki A, et al. (2016) Partial Contribution of the Keap1-Nrf2 System to Cadmium-Mediated Metallothionein Expression in Vascular Endothelial Cells. Toxicol Appl Pharmacol 295:37-46 doi:10.1016/j.taap.2016.01.020

Smith CJ, Perfetti TA, Rumple MA, Rodgman A, Doolittle DJ (2000) "IARC group 2A Carcinogens" reported in cigarette mainstream smoke. Food Chem Toxicol 38(4):371-83 doi:10.1016/s0278-6915(99)00156-8

Smith EA, Oehme FW (1991) Acrylamide and polyacrylamide: a review of production, use, environmental fate and neurotoxicity. Rev Environ Health 9(4):215-28 doi:10.1515/reveh.1991.9.4.215

Spencer PS, Schaumburg HH (1974) A review of acrylamide neurotoxicity. Part II. Experimental animal neurotoxicity and pathologic mechanisms. Can J Neurol Sci 1(3):152-69 doi:10.1017/s0317167100119201

Stadler RH, Blank I, Varga N, et al. (2002) Acrylamide from Maillard reaction products. Nature 419(6906):449-450 doi:10.1038/419449a

Streit WJ (2006) Microglial senescence: does the brain's immune system have an expiration date? Trends Neurosci 29(9):506-10 doi:10.1016/j.tins.2006.07.001

Streit WJ, Sammons NW, Kuhns AJ, Sparks DL (2004) Dystrophic microglia in the aging human brain. Glia 45(2):208-12 doi:10.1002/glia.10319

Subramanian K, Mohideen SS, Suzumura A, et al. (2012) Exposure to 1-bromopropane induces microglial changes and oxidative stress in the rat cerebellum. Toxicology 302(1):18-24 doi:10.1016/j.tox.2012.07.006

Sumi D (2008) Biological Effects of and Responses to Exposure to Electrophilic Environmental Chemicals. J Health Sci 54(3):267-272 doi:10.1248/jhs.54.267

Sun Y, Yang T, Mao L, Zhang F (2017) Sulforaphane Protects against Brain Diseases: Roles of Cytoprotective Enzymes. Austin J Cerebrovasc Dis Stroke 4(1) doi:10.26420/austinjcerebrovascdisstroke.2017.1054

Suzuki K, Pfaff LD (1973) Acrylamide neuropathy in rats. An electron microscopic study of degeneration and regeneration. Acta Neuropathol 24(3):197-213 doi:10.1007/bf00687590

Suzuki T, Muramatsu A, Saito R, et al. (2019) Molecular Mechanism of Cellular Oxidative Stress Sensing by Keap1. Cell Rep 28(3):746-758.e4 doi:10.1016/j.celrep.2019.06.047

Takahashi E, Niimi K, Itakura C (2009) Motor coordination impairment in aged heterozygous rolling Nagoya, Cav2.1 mutant mice. Brain Res 1279:50-7 doi:10.1016/j.brainres.2009.05.016

Takahashi J, Shibata T, Sasaki M, et al. (2015) Detection of changes in the locus coeruleus in patients with mild cognitive impairment and Alzheimer's disease: high-resolution fast spin- echo T1-weighted imaging. Geriatr Gerontol Int 15(3):334-40 doi:10.1111/ggi.12280

Tang Y, Le W (2014) “Good” and “Bad” Microglia in Parkinson’s Disease: An Understanding of Homeostatic Mechanisms in Immunomodulation Inflammation in Parkinson's Disease. Springer International Publishing, p 105-126

Tanii H, Hashimoto K (1983) Neurotoxicity of acrylamide and related compounds in rats. Effects on rotarod performance, morphology of nerves and neurotubulin. Arch Toxicol 54(3):203-13 doi:10.1007/bf01239204

Tansey MG, McCoy MK, Frank-Cannon TC (2007) Neuroinflammatory mechanisms in Parkinson's disease: Potential environmental triggers, pathways, and targets for early therapeutic intervention. Exp Neurol 208(1):1-25 doi:10.1016/j.expneurol.2007.07.004

Tao S, Rojo de la Vega M, Quijada H, et al. (2016) Bixin protects mice against ventilation-induced lung injury in an NRF2-dependent manner. Scientific Reports 6(1):18760 doi:10.1038/srep18760

Tareke E, Rydberg P, Karlsson P, Eriksson S, Törnqvist M (2000) Acrylamide: A Cooking Carcinogen? Chem Res Toxicol 13(6):517-522 doi:doi: 10.1021/tx9901938

Tareke E, Rydberg P, Karlsson P, Eriksson S, Törnqvist M (2002) Analysis of Acrylamide, a Carcinogen Formed in Heated Foodstuffs. J Agric Food Chem 50(17):4998-5006 doi:10.1021/jf020302f

Tarozzi A, Angeloni C, Malaguti M, Morroni F, Hrelia S, Hrelia P (2013) Sulforaphane as a potential protective phytochemical against neurodegenerative diseases. Oxid Med Cell Longev 2013:415078 doi:10.1155/2013/415078

Tarozzi A, Morroni F, Merlicco A, et al. (2009) Sulforaphane as an inducer of glutathione prevents oxidative stress-induced cell death in a dopaminergic-like neuroblastoma cell line. J Neurochem 111(5):1161-71 doi:10.1111/j.1471-4159.2009.06394.x

Taylor JP, Hardy J, Fischbeck KH (2002) Toxic Proteins in Neurodegenerative Disease. Science 296(5575):1991-1995 doi:10.1126/science.1067122

Tejani-Butt SM, Yang J, Zaffar H (1993) Norepinephrine transporter sites are decreased in the locus coeruleus in Alzheimer's disease. Brain Res 631(1):147-150 doi:10.1016/0006- 8993(93)91201-3

Thirumoorthy N, Shyam Sunder A, Manisenthil Kumar K, Senthil Kumar M, Ganesh G, Chatterjee M (2011) A review of metallothionein isoforms and their role in pathophysiology. World J Surg Oncol 9:54 doi:10.1186/1477-7819-9-54

Timmermann L, Ploner M, Haucke K, Schmitz F, Baltissen R, Schnitzler A (2001) Differential coding of pain intensity in the human primary and secondary somatosensory cortex. J Neurophysiol 86(3):1499-503 doi:10.1152/jn.2001.86.3.1499

Tonelli C, Chio IIC, Tuveson DA (2018) Transcriptional Regulation by Nrf2. Antioxid Redox Signal 29(17):1727-1745 doi:10.1089/ars.2017.7342

Town T, Nikolic V, Tan J (2005) The microglial "activation" continuum: from innate to adaptive responses. J Neuroinflammation 2:24 doi:10.1186/1742-2094-2-24

Toyama T, Shinkai Y, Yasutake A, Uchida K, Yamamoto M, Kumagai Y (2011) Isothiocyanates Reduce Mercury Accumulation via an Nrf2-dependent Mechanism During Exposure of Mice to Methylmercury. Environ Health Perspect 119(8):1117-22 doi:10.1289/ehp.1003123

Toyama T, Sumi D, Shinkai Y, et al. (2007) Cytoprotective Role of Nrf2/Keap1 System in Methylmercury Toxicity. Biochem Biophys Res Commun 363(3):645-50 doi:10.1016/j.bbrc.2007.09.017

Tyl R, Marr MC, Myers CB, Ross WP, Friedman MA (2000) Relationship between acrylamide reproductive and neurotoxicity in male rats. Reprod Toxicol 14(2):147-157 doi:10.1016/s0890-6238(00)00066-6

Tyl RW, Friedman MA (2003) Effects of acrylamide on rodent reproductive performance. Reprod Toxicol 17(1):1-13 doi:10.1016/s0890-6238(02)00078-3

United States Environmental Protection Agency USEPA (1996) Health Effects Test Guidelines. OPPTS 870.6200. Neurotoxicity Screening Battery. Environmental Protection Agency, Publication Washington D.C.

Vallee BL (1987) Implications and inferences of metallothionein structure. Experientia Suppl 52:5- 16 doi:10.1007/978-3-0348-6784-9_1

Van De Werd HJ, Rajkowska G, Evers P, Uylings HB (2010) Cytoarchitectonic and chemoarchitectonic characterization of the prefrontal cortical areas in the mouse. Brain Struct Funct 214(4):339-53 doi:10.1007/s00429-010-0247-z

Varnum MM, Ikezu T (2012) The Classification of Microglial Activation Phenotypes on Neurodegeneration and Regeneration in Alzheimer’s Disease Brain. Arch Immunol Ther Exp (Warsz) 60(4):251-266 doi:10.1007/s00005-012-0181-2

Verschueren K (2001) Handbook of environmental data on organic chemicals, vol 1-2, 4th edn. John Wiley & Sons, Incorporated, New York, NY

Vomund S, Schäfer A, Parnham MJ, Brüne B, von Knethen A (2017) Nrf2, the Master Regulator of Anti-Oxidative Responses. Int J Mol Sci 18(12) doi:10.3390/ijms18122772

Wakabayashi N, Dinkova-Kostova AT, Holtzclaw WD, et al. (2004) Protection against electrophile and oxidant stress by induction of the phase 2 response: fate of cysteines of the Keap1 sensor modified by inducers. Proc Natl Acad Sci U S A 101(7):2040-5 doi:10.1073/pnas.0307301101

Waza AA, Hamid Z, Ali S, Bhat SA, Bhat MA (2018) A review on heme oxygenase-1 induction: is it a necessary evil. Inflamm Res 67(7):579-588 doi:10.1007/s00011-018-1151-x

WHO (2002) Health Implications of Acrylamide in Food: Report of a Joint FAO/WHO Consultation. World Health Organization, Geneva, Switzerland, p 1-35

Wise SP (2008) Forward frontal fields: phylogeny and fundamental function. Trends Neurosci 31(12):599-608 doi:10.1016/j.tins.2008.08.008

Wolpert D, Pearson K, Ghez C (2013) The organization and planning of movement. In: Kandel E, Schwartz J, Jessell T, Seigelbaum S, Hudspeth A (eds) Principles of Neural Science. 5th edn. McGraw-Hill Companies, New York, p 743–767

Wood JN, Grafman J (2003) Human prefrontal cortex: processing and representational perspectives. Nat Rev Neurosci 4(2):139-47 doi:10.1038/nrn1033

Wood JN, Romero SG, Makale M, Grafman J (2003) Category-specific representations of social and nonsocial knowledge in the human prefrontal cortex. J Cogn Neurosci 15(2):236-48 doi:10.1162/089892903321208178

Wu H, Kong L, Cheng Y, et al. (2015) Metallothionein plays a prominent role in the prevention of diabetic nephropathy by sulforaphane via up-regulation of Nrf2. Free Radic Biol Med 89:431-42 doi:10.1016/j.freeradbiomed.2015.08.009

Yates MS, Tran QT, Dolan PM, et al. (2009) Genetic versus chemoprotective activation of Nrf2 signaling: overlapping yet distinct gene expression profiles between Keap1 knockout and triterpenoid-treated mice. Carcinogenesis 30(6):1024-1031 doi:10.1093/carcin/bgp100

Yehuda H, Soroka Y, Zlotkin-Frušić M, Gilhar A, Milner Y, Tamir S (2012) Isothiocyanates inhibit psoriasis-related proinflammatory factors in human skin. Inflamm Res 61(7):735-42 doi:10.1007/s00011-012-0465-3

Yuki K, Yoshida T, Miyake S, Tsubota K, Ozawa Y (2013) Neuroprotective role of superoxide dismutase 1 in retinal ganglion cells and inner nuclear layer cells against N-methyl-d- aspartate-induced cytotoxicity. Exp Eye Res 115:230-8 doi:10.1016/j.exer.2013.07.002

Zhang DD, Hannink M (2003) Distinct Cysteine Residues in Keap1 Are Required for Keap1- Dependent Ubiquitination of Nrf2 and for Stabilization of Nrf2 by Chemopreventive Agents and Oxidative Stress. Mol Cell Biol 23(22):8137-8151 doi:10.1128/mcb.23.22.8137- 8151.2003

Zhang DD, Lo S-C, Cross JV, Templeton DJ, Hannink M (2004) Keap1 Is a Redox-Regulated Substrate Adaptor Protein for a Cul3-Dependent Ubiquitin Ligase Complex. Mol Cell Biol 24(24):10941-10953 doi:10.1128/mcb.24.24.10941-10953.2004

Zhang L, Gavin T, Barber DS, LoPachin RM (2011) Role of the Nrf2-ARE pathway in acrylamide neurotoxicity. Toxicol Lett 205(1):1-7 doi:10.1016/j.toxlet.2011.04.011

Zhang L, Hara S, Ichinose H, et al. (2020) Exposure to acrylamide decreases noradrenergic axons in rat brain. Neurotoxicology 78:127-133 doi:10.1016/j.neuro.2020.03.001

Zhang Y, Talalay P, Cho CG, Posner GH (1992) A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proc Natl Acad Sci U S A 89(6):2399-403 doi:10.1073/pnas.89.6.2399

Zhou Q, Chen B, Wang X, et al. (2016) Sulforaphane protects against rotenone-induced neurotoxicity in vivo: Involvement of the mTOR, Nrf2, and autophagy pathways. Sci Rep 6:32206 doi:10.1038/srep32206

Zhu JW, Li YF, Wang ZT, Jia WQ, Xu RX (2016) Toll-Like Receptor 4 Deficiency Impairs Motor Coordination. Front Neurosci 10:33 doi:10.3389/fnins.2016.00033

Zong C, Hasegawa R, Urushitani M, et al. (2019) Role of microglial activation and neuroinflammation in neurotoxicity of acrylamide in vivo and in vitro. Arch Toxicol 93(7):2007-2019 doi:10.1007/s00204-019-02471-0