Skip to main content

Advertisement

Log in

Mitochondrial mechanisms of redox cycling agents implicated in Parkinson’s disease

  • Translational Neurosciences - Review article
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

Environmental agents have been implicated in Parkinson’s disease (PD) based on epidemiological studies and the ability of toxicants to replicate features of PD. However, the precise mechanisms by which toxicants induce dopaminergic toxicity observed in the idiopathic form of PD remain to be fully understood. The roles of ROS and mitochondria are strongly suggested in the mechanisms by which these toxicants exert dopaminergic toxicity. There are marked differences and similarities shared by the toxicants in increasing steady-state levels of mitochondrial ROS. Furthermore, toxicants increase steady-state mitochondrial ROS levels by stimulating the production, inhibiting the antioxidant pathways of both. This review will focus on the role of mitochondria and ROS in PD associated with environmental exposures to redox-based toxicants.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Abou-Sleiman PM, Muqit MM, Wood NW (2006) Expanding insights of mitochondrial dysfunction in Parkinson’s disease. Nat Rev Neurosci 7:207–219

    Article  CAS  PubMed  Google Scholar 

  • Adams JD, Klaidman LK, Cadenas E (1992) MPP+ redox cycling: a new mechanism involving hydride transfer. Ann N Y Acad Sci 648:239–240

    Article  CAS  PubMed  Google Scholar 

  • Ahmadi FA, Linseman DA, Grammatopoulos TN, Jones SM, Bouchard RJ, Freed CR, Heidenreich KA, Zawada WM (2003) The pesticide rotenone induces caspase-3-mediated apoptosis in ventral mesencephalic dopaminergic neurons. J Neurochem 87:914–921

    Article  CAS  PubMed  Google Scholar 

  • Bains JS, Shaw CA (1997) Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death. Brain Res Brain Res Rev 25:335–358

    Article  CAS  PubMed  Google Scholar 

  • Barlow BK, Lee DW, Cory-Slechta DA, Opanashuk LA (2005) Modulation of antioxidant defense systems by the environmental pesticide maneb in dopaminergic cells. Neurotoxicology 26:63–75

    Article  CAS  PubMed  Google Scholar 

  • Baynes JW (1991) Role of oxidative stress in development of complications in diabetes. Diabetes 40:405–412

    Article  CAS  PubMed  Google Scholar 

  • Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT (2000) Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 3:1301–1306

    Article  CAS  PubMed  Google Scholar 

  • Betarbet R, Sherer TB, Greenamyre JT (2002) Animal models of Parkinson’s disease. BioEssays 24:308–318

    Article  CAS  PubMed  Google Scholar 

  • Blum D, Torch S, Lambeng N, Nissou M, Benabid AL, Sadoul R, Verna JM (2001) Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson’s disease. Prog Neurobiol 65:135–172

    Article  CAS  PubMed  Google Scholar 

  • Bonneh-Barkay D, Reaney SH, Langston WJ, Di Monte DA (2005) Redox cycling of the herbicide paraquat in microglial cultures. Brain Res Mol Brain Res 134:52–56

    Article  CAS  PubMed  Google Scholar 

  • Bove J, Perier C (2012) Neurotoxin-based models of Parkinson’s disease. Neuroscience 211:51–76

    Article  CAS  PubMed  Google Scholar 

  • Boveris A, Chance B (1973) The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Biochem J 134:707–716

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Brooks AI, Chadwick CA, Gelbard HA, Cory-Slechta DA, Federoff HJ (1999) Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss. Brain Res 823:1–10

    Article  CAS  PubMed  Google Scholar 

  • Cadenas E, Davies KJ (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 29:222–230

    Article  CAS  PubMed  Google Scholar 

  • Callio J, Oury TD, Chu CT (2005) Manganese superoxide dismutase protects against 6-hydroxydopamine injury in mouse brains. J Biol Chem 280:18536–18542

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Castello PR, Drechsel DA, Patel M (2007) Mitochondria are a major source of paraquat-induced reactive oxygen species production in the brain. J Biol Chem 282:14186–14193

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chacon JN, Chedekel MR, Land EJ, Truscott TG (1987) Chemically induced Parkinson’s disease: intermediates in the oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to the 1-methyl-4-phenyl-pyridinium ion. Biochem Biophys Res Commun 144:957–964

    Article  CAS  PubMed  Google Scholar 

  • Chandel NS, Budinger GR (2007) The cellular basis for diverse responses to oxygen. Free Radic Biol Med 42:165–174

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Cai J, Murphy TJ, Jones DP (2002) Overexpressed human mitochondrial thioredoxin confers resistance to oxidant-induced apoptosis in human osteosarcoma cells. J Biol Chem 277:33242–33248

    Article  CAS  PubMed  Google Scholar 

  • Cherubini A, Ruggiero C, Polidori MC, Mecocci P (2005) Potential markers of oxidative stress in stroke. Free Radic Biol Med 39:841–852

    Article  CAS  PubMed  Google Scholar 

  • Cicchetti F, Drouin-Ouellet J, Gross RE (2009) Environmental toxins and Parkinson’s disease: what have we learned from pesticide-induced animal models? Trends Pharmacol Sci 30:475–483

    Article  CAS  PubMed  Google Scholar 

  • Cleeter MW, Cooper JM, Schapira AH (1992) Irreversible inhibition of mitochondrial complex I by 1-methyl-4-phenylpyridinium: evidence for free radical involvement. J Neurochem 58:786–789

    Article  CAS  PubMed  Google Scholar 

  • Clejan L, Cederbaum AI (1989) Synergistic interactions between NADPH-cytochrome P-450 reductase, paraquat, and iron in the generation of active oxygen radicals. Biochem Pharmacol 38:1779–1786

    Article  CAS  PubMed  Google Scholar 

  • Collins Y, Chouchani ET, James AM, Menger KE, Cocheme HM, Murphy MP (2012) Mitochondrial redox signalling at a glance. J Cell Sci 125:801–806

    Article  CAS  PubMed  Google Scholar 

  • Conrad M, Jakupoglu C, Moreno SG, Lippl S, Banjac A, Schneider M, Beck H, Hatzopoulos AK, Just U, Sinowatz F, Schmahl W, Chien KR, Wurst W, Bornkamm GW, Brielmeier M (2004) Essential role for mitochondrial thioredoxin reductase in hematopoiesis, heart development, and heart function. Mol Cell Biol 24:9414–9423

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Costello S, Cockburn M, Bronstein J, Zhang X, Ritz B (2009) Parkinson’s disease and residential exposure to maneb and paraquat from agricultural applications in the central valley of California. Am J Epidemiol 169:919–926

    Article  PubMed Central  PubMed  Google Scholar 

  • Curtius HC, Wolfensberger M, Steinmann B, Redweik U, Siegfried J (1974) Mass fragmentography of dopamine and 6-hydroxydopamine. Application to the determination of dopamine in human brain biopsies from the caudate nucleus. J Chromatogr 99:529–540

    Article  CAS  PubMed  Google Scholar 

  • Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39:889–909

    Article  CAS  PubMed  Google Scholar 

  • Dawson TM, Dawson VL (2003) Rare genetic mutations shed light on the pathogenesis of Parkinson disease. J Clin Invest 111:145–151

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Day BJ, Shawen S, Liochev SI, Crapo JD (1995) A metalloporphyrin superoxide dismutase mimetic protects against paraquat-induced endothelial cell injury, in vitro. J Pharmacol Exp Ther 275:1227–1232

    CAS  PubMed  Google Scholar 

  • Day BJ, Patel M, Calavetta L, Chang LY, Stamler JS (1999) A mechanism of paraquat toxicity involving nitric oxide synthase. Proc Natl Acad Sci USA 96:12760–12765

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Deumens R, Blokland A, Prickaerts J (2002) Modeling Parkinson’s disease in rats: an evaluation of 6-OHDA lesions of the nigrostriatal pathway. Exp Neurol 175:303–317

    Article  CAS  PubMed  Google Scholar 

  • Dhillon AS, Tarbutton GL, Levin JL, Plotkin GM, Lowry LK, Nalbone JT, Shepherd S (2008) Pesticide/environmental exposures and Parkinson’s disease in East Texas. J Agromedicine 13:37–48

    Article  PubMed  Google Scholar 

  • Dickinson DA, Forman HJ (2002) Cellular glutathione and thiols metabolism. Biochem Pharmacol 64:1019–1026

    Article  CAS  PubMed  Google Scholar 

  • Dinis-Oliveira RJ, Remiao F, Carmo H, Duarte JA, Navarro AS, Bastos ML, Carvalho F (2006) Paraquat exposure as an etiological factor of Parkinson’s disease. Neurotoxicology 27:1110–1122

    Article  CAS  PubMed  Google Scholar 

  • Domico LM, Zeevalk GD, Bernard LP, Cooper KR (2006) Acute neurotoxic effects of mancozeb and maneb in mesencephalic neuronal cultures are associated with mitochondrial dysfunction. Neurotoxicology 27:816–825

    Article  CAS  PubMed  Google Scholar 

  • Drechsel DA, Patel M (2008) Role of reactive oxygen species in the neurotoxicity of environmental agents implicated in Parkinson’s disease. Free Radic Biol Med 44:1873–1886

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Drechsel DA, Patel M (2009a) Chapter 21 paraquat-induced production of reactive oxygen species in brain mitochondria. Methods Enzymol 456:381–393

    Article  CAS  PubMed  Google Scholar 

  • Drechsel DA, Patel M (2009b) Differential contribution of the mitochondrial respiratory chain complexes to reactive oxygen species production by redox cycling agents implicated in parkinsonism. Toxicol Sci 112:427–434

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Drechsel DA, Patel M (2010) Respiration-dependent H2O2 removal in brain mitochondria via the thioredoxin/peroxiredoxin system. J Biol Chem 285:27850–27858

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fahn S (2003) Description of Parkinson’s disease as a clinical syndrome. Ann N Y Acad Sci 991:1–14

    Article  CAS  PubMed  Google Scholar 

  • Fahn S, Sulzer D (2004) Neurodegeneration and neuroprotection in Parkinson disease. NeuroRx 1:139–154

    Article  PubMed Central  PubMed  Google Scholar 

  • Floor E, Wetzel MG (1998) Increased protein oxidation in human substantia nigra pars compacta in comparison with basal ganglia and prefrontal cortex measured with an improved dinitrophenylhydrazine assay. J Neurochem 70:268–275

    Article  CAS  PubMed  Google Scholar 

  • Forno LS, DeLanney LE, Irwin I, Langston JW (1996) Electron microscopy of Lewy bodies in the amygdala-parahippocampal region. Comparison with inclusion bodies in the MPTP-treated squirrel monkey. Adv Neurol 69:217–228

    CAS  PubMed  Google Scholar 

  • Fukushima T, Yamada K, Isobe A, Shiwaku K, Yamane Y (1993) Mechanism of cytotoxicity of paraquat. I. NADH oxidation and paraquat radical formation via complex I. Exp Toxicol Pathol 45:345–349

    Article  CAS  PubMed  Google Scholar 

  • Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 114:1752–1761

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Giordano FJ (2005) Oxygen, oxidative stress, hypoxia, and heart failure. J Clin Invest 115:500–508

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gorell JM, Johnson CC, Rybicki BA, Peterson EL, Richardson RJ (1998) The risk of Parkinson’s disease with exposure to pesticides, farming, well water, and rural living. Neurology 50:1346–1350

    Article  CAS  PubMed  Google Scholar 

  • Graham DG (1984) Catecholamine toxicity: a proposal for the molecular pathogenesis of manganese neurotoxicity and Parkinson’s disease. Neurotoxicology 5:83–95

    CAS  PubMed  Google Scholar 

  • Grant H, Lantos PL, Parkinson C (1980) Cerebral damage in paraquat poisoning. Histopathology 4:185–195

    Article  CAS  PubMed  Google Scholar 

  • Guilarte TR (2010) Manganese and Parkinson’s disease: a critical review and new findings. Environ Health Perspect 118:1071–1080

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gutteridge JM, Halliwell B (2010) Antioxidants: molecules, medicines, and myths. Biochem Biophys Res Commun 393:561–564

    Article  CAS  PubMed  Google Scholar 

  • Haas RH, Nasirian F, Nakano K, Ward D, Pay M, Hill R, Shults CW (1995) Low platelet mitochondrial complex I and complex II/III activity in early untreated Parkinson’s disease. Ann Neurol 37:714–722

    Article  CAS  PubMed  Google Scholar 

  • Haller HL, Goodhue LD, Jones Howard A (1942) The constituents of derris and other rotenone-bearing plants. Chem Rev 30(1):33–48

    Article  CAS  Google Scholar 

  • Halliwell B, Gutteridge J (2007) Free radicals in biology and medicine, 4th edn. Oxford University Press, New York

    Google Scholar 

  • Hanschmann EM, Godoy JR, Berndt C, Hudemann C, Lillig CH (2013) Thioredoxins, glutaredoxins and peroxiredoxins—molecular mechanisms and health significance: from cofactors to antioxidants to redox signaling. Antioxid Redox Signal 19(13):1539–1605

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hasegawa E, Takeshige K, Oishi T, Murai Y, Minakami S (1990) 1-Methyl-4-phenylpyridinium (MPP+) induces NADH-dependent superoxide formation and enhances NADH-dependent lipid peroxidation in bovine heart submitochondrial particles. Biochem Biophys Res Commun 170:1049–1055

    Article  CAS  PubMed  Google Scholar 

  • Heikkila RE, Hess A, Duvoisin RC (1984) Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine in mice. Science 224:1451–1453

    Article  CAS  PubMed  Google Scholar 

  • Henchcliffe C, Beal MF (2008) Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis. Nat Clin Pract Neurol 4:600–609

    Article  CAS  PubMed  Google Scholar 

  • Hertzman C, Wiens M, Bowering D, Snow B, Calne D (1990) Parkinson’s disease: a case-control study of occupational and environmental risk factors. Am J Ind Med 17:349–355

    Article  CAS  PubMed  Google Scholar 

  • Hughes JT (1988) Brain damage due to paraquat poisoning: a fatal case with neuropathological examination of the brain. Neurotoxicology 9:243–248

    CAS  PubMed  Google Scholar 

  • Javitch JA, D’Amato RJ, Strittmatter SM, Snyder SH (1985) Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. Proc Natl Acad Sci USA 82:2173–2177

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jomova K, Valko M (2011) Advances in metal-induced oxidative stress and human disease. Toxicology 283:65–87

    Article  CAS  PubMed  Google Scholar 

  • Jones DP, Go YM (2010) Redox compartmentalization and cellular stress. Diabetes Obes Metab 12(Suppl 2):116–125

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jones GM, Vale JA (2000) Mechanisms of toxicity, clinical features, and management of diquat poisoning: a review. J Toxicol Clin Toxicol 38:123–128

    Article  CAS  PubMed  Google Scholar 

  • Kachroo A, Irizarry MC, Schwarzschild MA (2010) Caffeine protects against combined paraquat and maneb-induced dopaminergic neuron degeneration. Exp Neurol 223:657–661

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Karuppagounder SS, Ahuja M, Buabeid M, Parameshwaran K, Abdel-Rehman E, Suppiramaniam V, Dhanasekaran M (2012) Investigate the chronic neurotoxic effects of diquat. Neurochem Res 37:1102–1111

    Article  CAS  PubMed  Google Scholar 

  • Klaidman LK, Adams JD Jr, Leung AC, Kim SS, Cadenas E (1993) Redox cycling of MPP+: evidence for a new mechanism involving hydride transfer with xanthine oxidase, aldehyde dehydrogenase, and lipoamide dehydrogenase. Free Radic Biol Med 15:169–179

    Article  CAS  PubMed  Google Scholar 

  • Kulich SM, Horbinski C, Patel M, Chu CT (2007) 6-Hydroxydopamine induces mitochondrial ERK activation. Free Radic Biol Med 43:372–383

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lang AE, Lozano AM (1998) Parkinson’s disease. First of two parts. N Engl J Med 339:1044–1053

    Article  CAS  PubMed  Google Scholar 

  • Lang CA, Wu WK, Chen T, Mills BJ (1989) Blood glutathione: a biochemical index of life span enhancement in the diet restricted Lobund-Wistar rat. Prog Clin Biol Res 287:241–246

    CAS  PubMed  Google Scholar 

  • Langston JW, Ballard P, Tetrud JW, Irwin I (1983) Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219:979–980

    Article  CAS  PubMed  Google Scholar 

  • Liang LP, Kavanagh TJ, Patel M (2013) Glutathione deficiency in Gclm null mice results in complex I inhibition and dopamine depletion following paraquat administration. Toxicol Sci 134:366–373

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795

    Article  CAS  PubMed  Google Scholar 

  • Liou HH, Tsai MC, Chen CJ, Jeng JS, Chang YC, Chen SY, Chen RC (1997) Environmental risk factors and Parkinson’s disease: a case-control study in Taiwan. Neurology 48:1583–1588

    Article  CAS  PubMed  Google Scholar 

  • Logroscino G (2005) The role of early life environmental risk factors in Parkinson disease: what is the evidence? Environ Health Perspect 113:1234–1238

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lomaestro BM, Malone M (1995) Glutathione in health and disease: pharmacotherapeutic issues. Ann Pharmacother 29:1263–1273

    CAS  PubMed  Google Scholar 

  • Lopert P, Day BJ, Patel M (2012) Thioredoxin reductase deficiency potentiates oxidative stress, mitochondrial dysfunction and cell death in dopaminergic cells. PLoS One 7:e50683

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Martin HL, Teismann P (2009) Glutathione–a review on its role and significance in Parkinson’s disease. Faseb J 23:3263–3272

    Article  CAS  PubMed  Google Scholar 

  • McCormack AL, Thiruchelvam M, Manning-Bog AB, Thiffault C, Langston JW, Cory-Slechta DA, Di Monte DA (2002) Environmental risk factors and Parkinson’s disease: selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat. Neurobiol Dis 10:119–127

    Article  CAS  PubMed  Google Scholar 

  • Morato GS, Lemos T, Takahashi RN (1989) Acute exposure to maneb alters some behavioral functions in the mouse. Neurotoxicol Teratol 11:421–425

    Article  CAS  PubMed  Google Scholar 

  • Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417:1–13

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nicklas WJ, Vyas I, Heikkila RE (1985) Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenyl-pyridine, a metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine. Life Sci 36:2503–2508

    Article  CAS  PubMed  Google Scholar 

  • Nonn L, Williams RR, Erickson RP, Powis G (2003) The absence of mitochondrial thioredoxin 2 causes massive apoptosis, exencephaly, and early embryonic lethality in homozygous mice. Mol Cell Biol 23:916–922

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Parker WD Jr, Boyson SJ, Parks JK (1989) Abnormalities of the electron transport chain in idiopathic Parkinson’s disease. Ann Neurol 26:719–723

    Article  PubMed  Google Scholar 

  • Parker WD Jr, Parks JK, Swerdlow RH (2008) Complex I deficiency in Parkinson’s disease frontal cortex. Brain Res 1189:215–218

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Parkinson J (2002) An essay on the shaking palsy. 1817. J Neuropsychiatry Clin Neurosci 14:223–236 (discussion 222)

    Article  PubMed  Google Scholar 

  • Patel M, Day BJ (1999) Metalloporphyrin class of therapeutic catalytic antioxidants. Trends Pharmacol Sci 20:359–364

    Article  CAS  PubMed  Google Scholar 

  • Perry TL, Godin DV, Hansen S (1982) Parkinson’s disease: a disorder due to nigral glutathione deficiency? Neurosci Lett 33:305–310

    Article  CAS  PubMed  Google Scholar 

  • Price LA, Newman KJ, Clague AE, Wilson PR, Wenck DJ (1995) Paraquat and diquat interference in the analysis of creatinine by the Jaffe reaction. Pathology 27:154–156

    Article  CAS  PubMed  Google Scholar 

  • Priyadarshi A, Khuder SA, Schaub EA, Priyadarshi SS (2001) Environmental risk factors and Parkinson’s disease: a metaanalysis. Environ Res 86:122–127

    Article  CAS  PubMed  Google Scholar 

  • Roede JR, Jones DP (2014) Thiol-reactivity of the fungicide maneb. Redox Biol 2:651–655

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Roede JR, Hansen JM, Go YM, Jones DP (2011) Maneb and paraquat-mediated neurotoxicity: involvement of peroxiredoxin/thioredoxin system. Toxicol Sci 121:368–375

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rybnikova E, Damdimopoulos AE, Gustafsson JA, Spyrou G, Pelto-Huikko M (2000) Expression of novel antioxidant thioredoxin-2 in the rat brain. Eur J Neurosci 12:1669–1678

    Article  CAS  PubMed  Google Scholar 

  • Sato S, Hattori N (2011) Genetic mutations and mitochondrial toxins shed new light on the pathogenesis of Parkinson’s disease. Parkinsons Dis 2011:979231

    PubMed Central  PubMed  Google Scholar 

  • Sechi GP, Agnetti V, Piredda M, Canu M, Deserra F, Omar HA, Rosati G (1992) Acute and persistent parkinsonism after use of diquat. Neurology 42:261–263

    Article  CAS  PubMed  Google Scholar 

  • Shastry BS (2003) Neurodegenerative disorders of protein aggregation. Neurochem Int 43:1–7

    Article  CAS  PubMed  Google Scholar 

  • Shaw CA, Pasqualotto BA, Curry K (1996) Glutathione-induced sodium currents in neocortex. NeuroReport 7:1149–1152

    Article  CAS  PubMed  Google Scholar 

  • Sheeran FL, Rydstrom J, Shakhparonov MI, Pestov NB, Pepe S (2010) Diminished NADPH transhydrogenase activity and mitochondrial redox regulation in human failing myocardium. Biochim Biophys Acta 1797:1138–1148

    Article  CAS  PubMed  Google Scholar 

  • Shimizu K, Ohtaki K, Matsubara K, Aoyama K, Uezono T, Saito O, Suno M, Ogawa K, Hayase N, Kimura K, Shiono H (2001) Carrier-mediated processes in blood–brain barrier penetration and neural uptake of paraquat. Brain Res 906:135–142

    Article  CAS  PubMed  Google Scholar 

  • Sian J, Dexter DT, Lees AJ, Daniel S, Agid Y, Javoy-Agid F, Jenner P, Marsden CD (1994) Alterations in glutathione levels in Parkinson’s disease and other neurodegenerative disorders affecting basal ganglia. Ann Neurol 36:348–355

    Article  CAS  PubMed  Google Scholar 

  • Smith LL (1982) Young scientists award lecture 1981: the identification of an accumulation system for diamines and polyamines into the lung and its relevance to paraquat toxicity. Arch Toxicol Suppl 5:1–14

    Article  PubMed  Google Scholar 

  • Smith Y, Wichmann T, Factor SA, DeLong MR (2011) Parkinson’s disease therapeutics: new developments and challenges since the introduction of levodopa. Neuropsychopharmacology 37:213–246

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Sofic E, Lange KW, Jellinger K, Riederer P (1992) Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson’s disease. Neurosci Lett 142:128–130

    Article  CAS  PubMed  Google Scholar 

  • Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M (1998) Alpha-synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies. Proc Natl Acad Sci USA 95:6469–6473

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Subramaniam SR, Chesselet MF (2013) Mitochondrial dysfunction and oxidative stress in Parkinson’s disease. Prog Neurobiol 106–107:17–32

    Article  PubMed  CAS  Google Scholar 

  • Tait SW, Green DR (2012) Mitochondria and cell signalling. J Cell Sci 125:807–815

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tanner CM, Kamel F, Ross GW, Hoppin JA, Goldman SM, Korell M, Marras C, Bhudhikanok GS, Kasten M, Chade AR, Comyns K, Richards MB, Meng C, Priestley B, Fernandez HH, Cambi F, Umbach DM, Blair A, Sandler DP, Langston JW (2011) Rotenone, paraquat, and Parkinson’s disease. Environ Health Perspect 119:866–872

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tomita M (1991) Comparison of one-electron reduction activity against the bipyridylium herbicides, paraquat and diquat, in microsomal and mitochondrial fractions of liver, lung and kidney (in vitro). Biochem Pharmacol 42:303–309

    Article  CAS  PubMed  Google Scholar 

  • Turrens JF (2003) Mitochondrial formation of reactive oxygen species. J Physiol 552:335–344

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Uversky VN (2004) Neurotoxicant-induced animal models of Parkinson’s disease: understanding the role of rotenone, maneb and paraquat in neurodegeneration. Cell Tissue Res 318:225–241

    Article  CAS  PubMed  Google Scholar 

  • Veal EA, Day AM, Morgan BA (2007) Hydrogen peroxide sensing and signaling. Mol Cell 26:1–14

    Article  CAS  PubMed  Google Scholar 

  • Yang Y, Dieter MZ, Chen Y, Shertzer HG, Nebert DW, Dalton TP (2002) Initial characterization of the glutamate-cysteine ligase modifier subunit Gclm(−/−) knockout mouse. Novel model system for a severely compromised oxidative stress response. J Biol Chem 277:49446–49452

    Article  CAS  PubMed  Google Scholar 

  • Yoritaka A, Hattori N, Uchida K, Tanaka M, Stadtman ER, Mizuno Y (1996) Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proc Natl Acad Sci U S A 93:2696–2701

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yoshino H, Nakagawa-Hattori Y, Kondo T, Mizuno Y (1992) Mitochondrial complex I and II activities of lymphocytes and platelets in Parkinson’s disease. J Neural Transm Park Dis Dement Sect 4:27–34

    Article  CAS  PubMed  Google Scholar 

  • Zeevalk GD, Razmpour R, Bernard LP (2008) Glutathione and Parkinson’s disease: is this the elephant in the room? Biomed Pharmacother 62:236–249

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Fitsanakis VA, Gu G, Jing D, Ao M, Amarnath V, Montine TJ (2003) Manganese ethylene-bis-dithiocarbamate and selective dopaminergic neurodegeneration in rat: a link through mitochondrial dysfunction. J Neurochem 84:336–346

    Article  CAS  PubMed  Google Scholar 

  • Ziemssen T, Reichmann H (2007) Non-motor dysfunction in Parkinson’s disease. Parkinsonism Relat Disord 13:323–332

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Manisha Patel.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lopert, P., Patel, M. Mitochondrial mechanisms of redox cycling agents implicated in Parkinson’s disease. J Neural Transm 123, 113–123 (2016). https://doi.org/10.1007/s00702-015-1386-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-015-1386-4

Keywords

Navigation