Skip to main content
SpringerLink
Log in

Links Between Paraquat and Parkinson’s Disease

  • Reference work entry
  • First Online:
Handbook of Neurotoxicity

  • 2844 Accesses

Abstract

Parkinson’s disease (PD) is currently regarded as the most common degenerative disorder of the aging brain after Alzheimer’s dementia. Much progress has been made in identifying the genes involved in familial, or inherited, PD. However, the majority of cases are sporadic (not inherited) and their origin(s) still remain largely undetermined. The environment is a key contributor to human health and disease. Epidemiological evidence suggests that environmental factors play a role in the etiology of neurodegenerative diseases. Particularly, paraquat (PQ) has been largely demonstrated to induce cell death in a variety of cell types and tissues associated with PD. The study of PQ-induced neurotoxicity has provided valuable insight into the mechanisms regulating neuronal cell death by environmental toxicants. However, to date, the molecular mechanisms involved in neuronal cell death by PQ have not been completely identified. This article presents a comprehensive review of the published epidemiologic and toxicologic literature and critically evaluates whether a relationship exists between PQ exposure and PD.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 549.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 549.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ARE:

Antioxidant responsive element

ASK1:

Apoptosis signal-regulating kinase 1

CMA:

Chaperone-mediated autophagy

DA:

Dopamine

DOPAC:

3,4-Dihydroxyphenylacetic acid

DβHB:

D-β-hydroxybutyrate

ER:

Endoplasmic reticulum

ERK:

Extracellular signal-regulated kinase

GSH:

Glutathione

HVA:

Homovanillic acid

IRE1:

Inositol-requiring enzyme 1

JNK:

c-Jun NH2-terminal kinase

LAMP-2A:

Lysosomal-associated membrane protein-2A

LD:

Lethal dose

MAO-B:

Monoamine oxidase B

Mn2+-EB-DTC:

Mn2+-ethylene-bis-dithiocarbamate

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Nrf2:

Nuclear factor (erythroid-derived 2)-like 2

PD:

Parkinson’s disease

PEG 400:

Polyethylene glycol 400

PKC:

Protein kinase C

PQ:

Paraquat

REP1:

Dinucleotide repeat sequence

ROS:

Reactive oxygen species

SAPK:

Stress-activated protein kinase

SOD:

Superoxide dismutase

TH:

Tyrosine hydroxylase

Trx:

Thioredoxin

WT:

Wild-type

References

  • Anichtchik, O. V., Kaslin, J., Peitsaro, N., Scheinin, M., & Panula, P. (2004). Neurochemical and behavioural changes in zebrafish Danio rerio after systemic administration of 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Journal of Neurochemistry, 88(2), 443–453.

    CAS  PubMed  Google Scholar 

  • Berry, C., La Vecchia, C., & Nicotera, P. (2010). Paraquat and Parkinson’s disease. Cell Death and Differentiation, 17(7), 1115–1125.

    CAS  PubMed  Google Scholar 

  • Bonifati, V., Rizzu, P., Squitieri, F., Krieger, E., Vanacore, N., van Swieten, J. C., Brice, A., van Duijn, C. M., Oostra, B., Meco, G., & Heutink, P. (2003). DJ-1 (PARK7), a novel gene for autosomal recessive, early onset parkinsonism. Neurological Science, 24(3), 159–160.

    CAS  Google Scholar 

  • Bonneh-Barkay, D., Langston, W. J., & Di Monte, D. A. (2005). Toxicity of redox cycling pesticides in primary mesencephalic cultures. Antioxidants & Redox Signaling, 7(5–6), 649–653.

    CAS  Google Scholar 

  • Braungart, E., Gerlach, M., Riederer, P., Baumeister, R., & Hoener, M. C. (2004). Caenorhabditis elegans MPP+ model of Parkinson’s disease for high-throughput drug screenings. Neurodegenerative Diseases, 1(4–5), 175–183.

    CAS  PubMed  Google Scholar 

  • Bretaud, S., Lee, S., & Guo, S. (2004). Sensitivity of zebrafish to environmental toxins implicated in Parkinson’s disease. Neurotoxicology and Teratology, 26(6), 857–864.

    CAS  PubMed  Google Scholar 

  • Brooks, A. I., Chadwick, C. A., Gelbard, H. A., Cory-Slechta, D. A., & Federoff, H. J. (1999). Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss. Brain Research, 823(1–2), 1–10.

    CAS  PubMed  Google Scholar 

  • Brown, T. P., Rumsby, P. C., Capleton, A. C., Rushton, L., & Levy, L. S. (2006). Pesticides and Parkinson’s disease–is there a link? Environmental Health Perspectives, 114(2), 156–164.

    PubMed Central  PubMed  Google Scholar 

  • Butterfield, P. G., Valanis, B. G., Spencer, P. S., Lindeman, C. A., & Nutt, J. G. (1993). Environmental antecedents of young-onset Parkinson’s disease. Neurology, 43(6), 1150–1158.

    CAS  PubMed  Google Scholar 

  • Calò, M., Iannöne, M., Passafaro, M., & Nisticò, G. (1990). Selective vulnerability of hippocampal CA3 neurones after microinfusion of paraquat into the rat substantia nigra or into the ventral tegmental area. Journal of Comparative Pathology, 103(1), 73–78.

    PubMed  Google Scholar 

  • Canet-Avilés, R. M., Wilson, M. A., Miller, D. W., Ahmad, R., McLendon, C., Bandyopadhyay, S., Baptista, M. J., Ringe, D., Petsko, G. A., & Cookson, M. R. (2004). The Parkinson’s disease protein DJ-1 is neuroprotective due to cysteine–sulfinic acid-driven mitochondrial localization. Proceedings of the National Academy of Sciences of the United States of America, 101(24), 9103–9108.

    PubMed Central  PubMed  Google Scholar 

  • Chau, K. Y., Korlipara, L. V., Cooper, J. M., & Schapira, A. H. (2009). Protection against paraquat and A53T alpha-synuclein toxicity by cabergoline is partially mediated by dopamine receptors. Journal of Neurological Sciences, 278(1–2), 44–53.

    CAS  Google Scholar 

  • Chau, K. Y., Cooper, J. M., & Schapira, A. H. (2010). Rasagiline protects against alpha-synuclein induced sensitivity to oxidative stress in dopaminergic cells. Neurochemistry International, 57(5), 525–529.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Choi, H. S., An, J. J., Kim, S. Y., Lee, S. H., Kim, D. W., Yoo, K. Y., Won, M. H., Kang, T. C., Kwon, H. J., Kang, J. H., Cho, S. W., Kwon, O. S., Park, J., Eum, W. S., & Choi, S. Y. (2006). PEP-1-SOD fusion protein efficiently protects against paraquat-induced dopaminergic neuron damage in a Parkinson disease mouse model. Free Radical Biology & Medicine, 41(7), 1058–1068.

    CAS  Google Scholar 

  • Chun, H. S., Gibson, G. E., DeGiorgio, L. A., Zhang, H., Kidd, V. J., & Son, J. H. (2001). Dopaminergic cell death induced by MPP(+), oxidant and specific neurotoxicants shares the common molecular mechanism. Journal of Neurochemistry, 76(4), 1010–1021.

    CAS  PubMed  Google Scholar 

  • Cicchetti, F., Lapointe, N., Roberge-Tremblay, A., Saint-Pierre, M., Jimenez, L., Ficke, B. W., & Gross, R. E. (2005). Systemic exposure to paraquat and maneb models early Parkinson’s disease in young adult rats. Neurobiology of Disease, 20(2), 360–371.

    CAS  PubMed  Google Scholar 

  • Corasaniti, M. T., Bagetta, G., Rodinò, P., Gratteri, S., & Nisticò, G. (1992). Neurotoxic effects induced by intracerebral and systemic injection of paraquat in rats. Human and Experimental Toxicology, 11(6), 535–539.

    CAS  PubMed  Google Scholar 

  • Corrigan, F. M., Murray, L., Wyatt, C. L., & Shore, R. F. (1998). Diorthosubstituted polychlorinated biphenyls in caudate nucleus in Parkinson’s disease. Experimental Neurology, 150(2), 339–342.

    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. American Journal of Epidemiology, 169(8), 919–926.

    PubMed Central  PubMed  Google Scholar 

  • Di Monte, D., Sandy, M. S., Ekström, G., & Smith, M. T. (1986). Comparative studies on the mechanisms of paraquat and 1-methyl-4-phenylpyridine (MPP+) cytotoxicity. Biochemical and Biophysical Research Communications, 137(1), 303–309.

    PubMed  Google Scholar 

  • Dinis-Oliveira, R. J., Remião, F., Carmo, H., Duarte, J. A., Navarro, A. S., Bastos, M. L., & Carvalho, F. (2006). Paraquat exposure as an etiological factor of Parkinson’s disease. Neurotoxicology, 27(6), 1110–1122.

    CAS  PubMed  Google Scholar 

  • Dinis-Oliveira, R. J., Duarte, J. A., Sánchez-Navarro, A., Remião, F., Bastos, M. L., & Carvalho, F. (2008). Paraquat poisonings: mechanisms of lung toxicity, clinical features, and treatment. Critical Reviews in Toxicology, 38(1), 13–71.

    CAS  PubMed  Google Scholar 

  • Drechsel, D. A., & Patel, M. (2008). Role of reactive oxygen species in the neurotoxicity of environmental agents implicated in Parkinson’s disease. Free Radical Biology & Medicine, 44(11), 1873–1886.

    CAS  Google Scholar 

  • Fei, Q., & Ethell, D. W. (2008). Maneb potentiates paraquat neurotoxicity by inducing key Bcl-2 family members. Journal of Neurochemistry, 105(6), 2091–2097.

    CAS  PubMed  Google Scholar 

  • Fei, Q., McCormack, A. L., Di Monte, D. A., & Ethell, D. W. (2008). Paraquat neurotoxicity is mediated by a Bak-dependent mechanism. Journal of Biological Chemistry, 283(6), 3357–3364.

    CAS  PubMed  Google Scholar 

  • Fernagut, P. O., Hutson, C. B., Fleming, S. M., Tetreaut, N. A., Salcedo, J., Masliah, E., & Chesselet, M. F. (2007). Behavioral and histopathological consequences of paraquat intoxication in mice: Effects of alpha-synuclein over-expression. Synapse, 61(12), 991–1001.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Firestone, J. A., Smith-Weller, T., Franklin, G., Swanson, P., Longstreth, W. T., Jr., & Checkoway, H. (2005). Pesticides and risk of Parkinson disease: A population-based case–control study. Archives of Neurology, 62(1), 91–95.

    PubMed  Google Scholar 

  • Fleming, L., Mann, J. B., Bean, J., Briggle, T., & Sánchez-Ramos, J. R. (1994). Parkinson’s disease and brain levels of organochlorine pesticides. Annals of Neurology, 36(1), 100–103.

    CAS  PubMed  Google Scholar 

  • Fujii, M., Matsumoto, Y., Tanaka, N., Miki, K., Suzuki, T., Ishii, N., & Ayusawa, D. (2004). Mutations in chemosensory cilia cause resistance to paraquat in nematode Caenorhabditis elegans. Journal of Biological Chemistry, 279(19), 20277–20282.

    CAS  PubMed  Google Scholar 

  • Fujii, M., Tanaka, N., Miki, K., Hossain, M. N., Endoh, M., & Ayusawa, D. (2005). Uncoupling of longevity and paraquat resistance in mutants of the nematode Caenorhabditis elegans. Bioscience, Biotechnology, and Biochemistry, 69(10), 2015–2018.

    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. Experimental and Toxicologic Pathology, 45(5–6), 345–349.

    CAS  PubMed  Google Scholar 

  • Gatto, N. M., Rhodes, S. L., Manthripragada, A. D., Bronstein, J., Cockburn, M., Farrer, M., & Ritz, B. (2010). Alpha-synuclein gene may interact with environmental factors in increasing risk of Parkinson’s disease. Neuroepidemiology, 35(3), 191–195.

    PubMed Central  PubMed  Google Scholar 

  • Gegg, M. E., Cooper, J. M., Schapira, A. H., & Taanman, J. W. (2009). Silencing of PINK1 expression affects mitochondrial DNA and oxidative phosphorylation in dopaminergic cells. PLoS One, 4(3), e4756.

    PubMed Central  PubMed  Google Scholar 

  • Goers, J., Manning-Bog, A. B., McCormack, A. L., Millett, I. S., Doniach, S., Di Monte, D. A., Uversky, V. N., & Fink, A. L. (2003). Nuclear localization of alpha-synuclein and its interaction with histones. Biochemistry, 42(28), 8465–8471.

    CAS  PubMed  Google Scholar 

  • González-Polo, R. A., Rodríguez-Martín, A., Morán, J. M., Niso, M., Soler, G., & Fuentes, J. M. (2004). Paraquat-induced apoptotic cell death in cerebellar granule cells. Brain Research, 1011(2), 170–176.

    PubMed  Google Scholar 

  • González-Polo, R. A., Niso-Santano, M., Ortíz-Ortíz, M. A., Gómez-Martín, A., Morán, J. M., García-Rubio, L., Francisco-Morcillo, J., Zaragoza, C., Soler, G., & Fuentes, J. M. (2007a). Inhibition of paraquat-induced autophagy accelerates the apoptotic cell death in neuroblastoma SH-SY5Y cells. Toxicological Sciences, 97(2), 448–458.

    PubMed  Google Scholar 

  • González-Polo, R. A., Niso-Santano, M., Ortíz-Ortíz, M. A., Gómez-Martín, A., Morán, J. M., García-Rubio, L., Francisco-Morcillo, J., Zaragoza, C., Soler, G., & Fuentes, J. M. (2007b). Relationship between autophagy and apoptotic cell death in human neuroblastoma cells treated with paraquat: Could autophagy be a “brake” in paraquat-induced apoptotic death? Autophagy, 3(4), 366–367.

    PubMed  Google Scholar 

  • González-Polo, R., Niso-Santano, M., Morán, J. M., Ortiz-Ortiz, M. A., Bravo-San Pedro, J. M., Soler, G., & Fuentes, J. M. (2009). Silencing DJ-1 reveals its contribution in paraquat-induced autophagy. Journal of Neurochemistry, 109(3), 889–898.

    PubMed  Google Scholar 

  • González-Polo, R. A., Niso-Santano, M., Gómez-Sánchez, R., Bravo-San Pedro, J. M., & Fuentes, J. M. (2010). DJ-1 as a modulator of autophagy: An hypothesis. The Scientific World Journal, 10, 1574–1579.

    Google Scholar 

  • Gorell, J. M., Peterson, E. L., Rybicki, B. A., & Johnson, C. C. (2004). Multiple risk factors for Parkinson’s disease. Journal of Neurological Sciences, 217(2), 169–174.

    Google Scholar 

  • Gray, J. P., Heck, D. E., Mishin, V., Smith, P. J., Hong, J. Y., Thiruchelvam, M., Cory-Slechta, D. A., Laskin, D. L., & Laskin, J. D. (2007). Paraquat increases cyanide-insensitive respiration in murine lung epithelial cells by activating an NAD(P)H: Paraquat oxidoreductase: Identification of the enzyme as thioredoxin reductase. Journal of Biological Chemistry, 282(11), 7939–7949.

    CAS  PubMed  Google Scholar 

  • Greene, J. C., Whitworth, A. J., Andrews, L. A., Parker, T. J., & Pallanck, L. J. (2005). Genetic and genomic studies of Drosophila parkin mutants implicate oxidative stress and innate immune responses in pathogenesis. Human Molecular Genetics, 14(6), 799–811.

    CAS  PubMed  Google Scholar 

  • Grimm, S., & Brdiczka, D. (2007). The permeability transition pore in cell death. Apoptosis, 12(5), 841–855.

    CAS  PubMed  Google Scholar 

  • Grünewald, A., Gegg, M. E., Taanman, J. W., King, R. H., Kock, N., Klein, C., & Schapira, A. H. (2009). Differential effects of PINK1 nonsense and missense mutations on mitochondrial function and morphology. Experimental Neurology, 219(1), 266–273.

    PubMed  Google Scholar 

  • Grünewald, A., Voges, L., Rakovic, A., Kasten, M., Vandebona, H., Hemmelmann, C., Lohmann, K., Orolicki, S., Ramirez, A., Schapira, A. H., Pramstaller, P. P., Sue, C. M., & Klein, C. (2010). Mutant Parkin impairs mitochondrial function and morphology in human fibroblasts. PLoS One, 5(9), e12962.

    PubMed Central  PubMed  Google Scholar 

  • Haley, T. J. (1979). Review of the toxicology of paraquat (1,1′-dimethyl-4,4′-bipyridinium chloride). Clinical Toxicology, 14(1), 1–46.

    CAS  PubMed  Google Scholar 

  • Hassan, R. A., Afzal, M., Ali, M., & Gubler, C. J. (1989). Effect of paraquat administered intraperitoneally on the nonpolar lipids of rabbits. Ecotoxicology and Environmental Safety, 17(1), 47–58.

    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. American Journal of Industrial Medicine, 17(3), 349–355.

    CAS  PubMed  Google Scholar 

  • Kamel, F., & Hoppin, J. A. (2004). Association of pesticide exposure with neurologic dysfunction and disease. Environmental Health Perspectives, 112(9), 950–958.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kamel, F., Tanner, C., Umbach, D., Hoppin, J., Alavanja, M., Blair, A., Comyns, K., Goldman, S., Korell, M., Langston, J., Ross, G., & Sandler, D. (2007). Pesticide exposure and self-reported Parkinson’s disease in the agricultural health study. American Journal of Epidemiology, 165(4), 364–374.

    CAS  PubMed  Google Scholar 

  • Kang, M. J., Gil, S. J., & Koh, H. C. (2009). Paraquat induces alternation of the dopamine catabolic pathways and glutathione levels in the substantia nigra of mice. Toxicology Letters, 188(2), 148–152.

    CAS  PubMed  Google Scholar 

  • Kim, S., Hwang, J., Lee, W. H., Hwang, D. Y., & Suk, K. (2008). Role of protein kinase Cdelta in paraquat-induced glial cell death. Journal of Neuroscience Research, 86(9), 2062–2070.

    CAS  PubMed  Google Scholar 

  • Kim, Y. H., Rane, A., Lussier, S., & Andersen, J. K. (2011). Lithium protects against oxidative stress-mediated cell death in alpha-synuclein-overexpressing in vitro and in vivo models of Parkinson’s disease. Journal of Neuroscience Research, 89(10), 1666–1675.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kinumi, T., Kimata, J., Taira, T., Ariga, H., & Niki, E. (2004). Cysteine-106 of DJ-1 is the most sensitive cysteine residue to hydrogen peroxide-mediated oxidation in vivo in human umbilical vein endothelial cells. Biochemical and Biophysical Research Communications, 317(3), 722–728.

    CAS  PubMed  Google Scholar 

  • Klintworth, H., Newhouse, K., Li, T., Choi, W. S., Faigle, R., & Xia, Z. (2007). Activation of c-Jun N-terminal protein kinase is a common mechanism underlying paraquat- and rotenone-induced dopaminergic cell apoptosis. Toxicological Sciences, 97(1), 149–162.

    CAS  PubMed  Google Scholar 

  • Langston, J. W., & Ballard, P. A., Jr. (1983). Parkinson’s disease in a chemist working with 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine. The New England Journal of Medicine, 309(5), 310.

    CAS  PubMed  Google Scholar 

  • Li, A. A., Mink, P. J., McIntosh, L. J., Teta, M. J., & Finley, B. (2005a). Evaluation of epidemiologic and animal data associating pesticides with Parkinson’s disease. Journal of Occupational and Environmental Medicine, 47(10), 1059–1087.

    PubMed  Google Scholar 

  • Li, X., Yin, J., Cheng, C. M., Sun, J. L., Li, Z., & Wu, Y. L. (2005b). Paraquat induces selective dopaminergic nigrostriatal degeneration in aging C57BL/6 mice. Chinese Medical Journal, 118(16), 1357–1361.

    CAS  PubMed  Google Scholar 

  • Liochev, S. I., Hausladen, A., Beyer, W. F., Jr., & Fridovich, I. (1994). NADPH: Ferredoxin oxidoreductase acts as a paraquat diaphorase and is a member of the soxRS regulon. Proceedings of the National Academy of Sciences of the United States of America, 91(4), 1328–1331.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Liou, H. H., Chen, R. C., Tsai, Y. F., Chen, W. P., Chang, Y. C., & Tsai, M. C. (1996). Effects of paraquat on the substantia nigra of the Wistar rats: Neurochemical, histological, and behavioral studies. Toxicology and Applied Pharmacology, 137(1), 34–41.

    CAS  PubMed  Google Scholar 

  • Liou, H. H., Tsai, M. C., Chen, C. J., Jeng, J. S., Chang, Y. C., Chen, S. Y., & Chen, R. C. (1997). Environmental risk factors and Parkinson’s disease: A case–control study in Taiwan. Neurology, 48(6), 1583–1588.

    CAS  PubMed  Google Scholar 

  • Mak, S. K., McCormack, A. L., Manning-Bog, A. B., Cuervo, A. M., & Di Monte, D. A. (2010). Lysosomal degradation of alpha-synuclein in vivo. Journal of Biological Chemistry, 285(18), 13621–13629.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Manning-Bog, A. B., McCormack, A. L., Li, J., Uversky, V. N., Fink, A. L., & Di Monte, D. A. (2002). The herbicide paraquat causes up-regulation and aggregation of alpha-synuclein in mice: Paraquat and alpha-synuclein. Journal of Biological Chemistry, 277(3), 1641–1644.

    CAS  PubMed  Google Scholar 

  • Manning-Bog, A. B., McCormack, A. L., Purisai, M. G., Bolin, L. M., & Di Monte, D. A. (2003). Alpha-synuclein overexpression protects against paraquat-induced neurodegeneration. Journal of Neuroscience, 23(8), 3095–3099.

    CAS  PubMed  Google Scholar 

  • Menzies, F. M., Yenisetti, S. C., & Min, K. T. (2005). Roles of Drosophila DJ-1 in survival of dopaminergic neurons and oxidative stress. Current Biology, 15(17), 1578–1582.

    CAS  PubMed  Google Scholar 

  • Menzies, F. M., Ravikumar, B., & Rubinsztein, D. C. (2006). Protective roles for induction of autophagy in multiple proteinopathies. Autophagy, 2(3), 224–225.

    CAS  PubMed  Google Scholar 

  • Miller, R. L., Sun, G. Y., & Sun, A. Y. (2007). Cytotoxicity of paraquat in microglial cells: Involvement of PKCdelta- and ERK1/2-dependent NADPH oxidase. Brain Research, 1167, 129–139.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Minelli, A., Conte, C., Grottelli, S., Bellezza, I., Emiliani, C., & Bolaños, J. P. (2009). Cyclo(His-Pro) up-regulates heme oxygenase 1 via activation of Nrf2-ARE signalling. Journal of Neurochemistry, 111(4), 956–966.

    CAS  PubMed  Google Scholar 

  • Munishkina, L. A., Cooper, E. M., Uversky, V. N., & Fink, A. L. (2004). The effect of macromolecular crowding on protein aggregation and amyloid fibril formation. Journal of Molecular Recognition, 17(5), 456–464.

    CAS  PubMed  Google Scholar 

  • Murray, R. E., & Gibson, J. E. (1972). A comparative study of paraquat intoxication in rats, guinea pigs and monkeys. Experimental and Molecular Pathology, 17(3), 317–325.

    CAS  PubMed  Google Scholar 

  • Nass, R., Miller, D. M., & Blakely, R. D. (2001). C. elegans: A novel pharmacogenetic model to study Parkinson’s disease. Parkinsonism & Related Disorders, 7(3), 185–191.

    Google Scholar 

  • Nass, R., Hall, D. H., Miller, D. M., 3rd, & Blakely, R. D. (2002). Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America, 99(5), 3264–3269.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Niso-Santano, M., Morán, J. M., García-Rubio, L., Gómez-Martín, A., González-Polo, R. A., Soler, G., & Fuentes, J. M. (2006). Low concentrations of paraquat induces early activation of extracellular signal-regulated kinase 1/2, protein kinase B, and c-Jun N-terminal kinase 1/2 pathways: Role of c-Jun N-terminal kinase in paraquat-induced cell death. Toxicological Sciences, 92(2), 507–515.

    CAS  PubMed  Google Scholar 

  • Niso-Santano, M., González-Polo, R. A., Bravo-San Pedro, J. M., Gómez-Sánchez, R., Lastres-Becker, I., Ortiz-Ortiz, M. A., Soler, G., Morán, J. M., Cuadrado, A., & Fuentes, J. M. (2010). Activation of apoptosis signal-regulating kinase 1 is a key factor in paraquat-induced cell death: Modulation by the Nrf2/Trx axis. Free Radical Biology & Medicine, 48(10), 1370–1381.

    CAS  Google Scholar 

  • Niso-Santano, M., Bravo-San Pedro, J. M., Gómez-Sánchez, R., Climent, V., Soler, G., Fuentes, J. M., & González-Polo, R. A. (2011). ASK1 overexpression accelerates paraquat-induced autophagy via endoplasmic reticulum stress. Toxicological Sciences, 119(1), 156–168.

    CAS  PubMed  Google Scholar 

  • Olanow, C. W. (2007). The pathogenesis of cell death in Parkinson’s disease–2007. Movement Disorders, 22(Suppl 17), S335–S342.

    PubMed  Google Scholar 

  • O’Leary, K. T., Parameswaran, N., Johnston, L. C., McIntosh, J. M., Di Monte, D. A., & Quik, M. (2008). Paraquat exposure reduces nicotinic receptor-evoked dopamine release in monkey striatum. Journal of Pharmacology and Experimental Therapeutics, 327(1), 124–129.

    PubMed Central  PubMed  Google Scholar 

  • Olesen, B. T., Clausen, J., & Vang, O. (2008). Characterization of the transcriptional profile in primary astrocytes after oxidative stress induced by paraquat. Neurotoxicology, 29(1), 13–21.

    CAS  PubMed  Google Scholar 

  • Orth, M., & Tabrizi, S. J. (2003). Models of Parkinson’s disease. Movement Disorders, 18(7), 729–737.

    PubMed  Google Scholar 

  • Orth, M., Tabrizi, S. J., Tomlinson, C., Messmer, K., Korlipara, L. V., Schapira, A. H., & Cooper, J. M. (2004). G209A mutant alpha synuclein expression specifically enhances dopamine induced oxidative damage. Neurochemistry International, 45(5), 669–676.

    CAS  PubMed  Google Scholar 

  • Pan, T., Kondo, S., Le, W., & Jankovic, J. (2008). The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson’s disease. Brain, 131(Pt 8), 1969–1978.

    PubMed  Google Scholar 

  • Patel, M., Day, B. J., Crapo, J. D., Fridovich, I., & McNamara, J. O. (1996). Requirement for superoxide in excitotoxic cell death. Neuron, 16(2), 345–355.

    CAS  PubMed  Google Scholar 

  • Peng, J., Mao, X. O., Stevenson, F. F., Hsu, M., & Andersen, J. K. (2004). The herbicide paraquat induces dopaminergic nigral apoptosis through sustained activation of the JNK pathway. Journal of Biological Chemistry, 279(31), 32626–32632.

    CAS  PubMed  Google Scholar 

  • Peng, J., Oo, M. L., & Andersen, J. K. (2010). Synergistic effects of environmental risk factors and gene mutations in Parkinson’s disease accelerate age-related neurodegeneration. Journal of Neurochemistry, 115(6), 1363–1373.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pesah, Y., Pham, T., Burgess, H., Middlebrooks, B., Verstreken, P., Zhou, Y., Harding, M., Bellen, H., & Mardon, G. (2004). Drosophila parkin mutants have decreased mass and cell size and increased sensitivity to oxygen radical stress. Development, 131(9), 2183–2194.

    CAS  PubMed  Google Scholar 

  • Prigione, A., Piazza, F., Brighina, L., Begni, B., Galbussera, A., Difrancesco, J. C., Andreoni, S., Piolti, R., & Ferrarese, C. (2010). Alpha-synuclein nitration and autophagy response are induced in peripheral blood cells from patients with Parkinson disease. Neuroscience Letters, 477(1), 6–10.

    CAS  PubMed  Google Scholar 

  • Purisai, M. G., McCormack, A. L., Cumine, S., Li, J., Isla, M. Z., & Di Monte, D. A. (2007). Microglial activation as a priming event leading to paraquat-induced dopaminergic cell degeneration. Neurobiology of Disease, 25(2), 392–400.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Purser, D. A., & Rose, M. S. (1979). The toxicity and renal handling of paraquat in cynomolgus monkeys. Toxicology, 15(1), 31–41.

    CAS  PubMed  Google Scholar 

  • Ramachandiran, S., Hansen, J. M., Jones, D. P., Richardson, J. R., & Miller, G. W. (2007). Divergent mechanisms of paraquat, MPP+, and rotenone toxicity: Oxidation of thioredoxin and caspase-3 activation. Toxicological Sciences, 95(1), 163–171.

    CAS  PubMed  Google Scholar 

  • Ravagnan, L., Roumier, T., & Kroemer, G. (2002). Mitochondria, the killer organelles and their weapons. Journal of Cellular Physiology, 192(2), 131–137.

    CAS  PubMed  Google Scholar 

  • Richardson, J. R., Quan, Y., Sherer, T. B., Greenamyre, J. T., & Miller, G. W. (2005). Paraquat neurotoxicity is distinct from that of MPTP and rotenone. Toxicological Sciences, 88(1), 193–201.

    CAS  PubMed  Google Scholar 

  • Röhrdanz, E., Schmuck, G., Ohler, S., & Kahl, R. (2001). The influence of oxidative stress on catalase and MnSOD gene transcription in astrocytes. Brain Research, 900(1), 128–136.

    PubMed  Google Scholar 

  • Rojo, A. I., Cavada, C., de Sagarra, M. R., & Cuadrado, A. (2007). Chronic inhalation of rotenone or paraquat does not induce Parkinson’s disease symptoms in mice or rats. Experimental Neurology, 208(1), 120–126.

    CAS  PubMed  Google Scholar 

  • Rossi, L., Marchese, E., Lombardo, M. F., Rotilio, G., & Ciriolo, M. R. (2001). Increased susceptibility of copper-deficient neuroblastoma cells to oxidative stress-mediated apoptosis. Free Radical Biology & Medicine, 30(10), 1177–1187.

    CAS  Google Scholar 

  • Rzezniczak, T. Z., Douglas, L. A., Watterson, J. H., & Merritt, T. J. (2011). Paraquat administration in Drosophila for use in metabolic studies of oxidative stress. Analytical Biochemistry, 419(2), 345–347.

    CAS  PubMed  Google Scholar 

  • Sämann, J., Hegermann, J., von Gromoff, E., Eimer, S., Baumeister, R., & Schmidt, E. (2009). Caenorhabditits elegans LRK-1 and PINK-1 act antagonistically in stress response and neurite outgrowth. Journal of Biological Chemistry, 284(24), 16482–16491.

    PubMed Central  PubMed  Google Scholar 

  • Schmuck, G., Röhrdanz, E., Tran-Thi, Q. H., Kahl, R., & Schlüter, G. (2002). Oxidative stress in rat cortical neurons and astrocytes induced by paraquat in vitro. Neurotoxicity Research, 4(1), 1–13.

    CAS  PubMed  Google Scholar 

  • Seidenfeld, J. J., Sobonya, R. E., & Toyoshima, J. M. (1985). Recovery from paraquat pneumonitis. British Journal of Industrial Medicine, 42(3), 178–183.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Seidler, A., Hellenbrand, W., Robra, B. P., Vieregge, P., Nischan, P., Joerg, J., Oertel, W. H., Ulm, G., & Schneider, E. (1996). Possible environmental, occupational, and other etiologic factors for Parkinson’s disease: A case–control study in Germany. Neurology, 46(5), 1275–1284.

    CAS  PubMed  Google Scholar 

  • Semchuk, K. M., Love, E. J., & Lee, R. G. (1992). Parkinson’s disease and exposure to agricultural work and pesticide chemicals. Neurology, 42(7), 1328–1335.

    CAS  PubMed  Google Scholar 

  • Somayajulu-Niţu, M., Sandhu, J. K., Cohen, J., Sikorska, M., Sridhar, T. S., Matei, A., Borowy-Borowski, H., & Pandey, S. (2009). Paraquat induces oxidative stress, neuronal loss in substantia nigra region and parkinsonism in adult rats: Neuroprotection and amelioration of symptoms by water-soluble formulation of coenzyme Q10. BMC Neuroscience, 10, 88.

    PubMed Central  PubMed  Google Scholar 

  • Sone, T., Talbot, A., Harada, T., Ikuo, T., Kato, T., & Uematsu, H. (1989). The effects of 24% paraquat (1,1′-dimethyl-4,4′-bipyridylium dichloride) on hemodynamics, blood gases, plasma lactate and plasma catecholamines in dogs. Veterinary and Human Toxicology, 31(2), 149–153.

    CAS  PubMed  Google Scholar 

  • Srikrishna, V., Riviere, J. E., & Monteiro-Riviere, N. A. (1992). Cutaneous toxicity and absorption of paraquat in porcine skin. Toxicology and Applied Pharmacology, 115(1), 89–97.

    CAS  PubMed  Google Scholar 

  • Taira, T., Saito, Y., Niki, T., Iguchi-Ariga, S. M., Takahashi, K., & Ariga, H. (2004). DJ-1 has a role in antioxidative stress to prevent cell death. EMBO Reports, 5(2), 213–218.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Takahashi, M., Kanuka, H., Fujiwara, H., Koyama, A., Hasegawa, M., Miura, M., & Iwatsubo, T. (2003). Phosphorylation of alpha-synuclein characteristic of synucleinopathy lesions is recapitulated in alpha-synuclein transgenic Drosophila. Neuroscience Letters, 336(3), 155–158.

    CAS  PubMed  Google Scholar 

  • Tanner, C. M., Kamel, F., Ross, G. W., Hoppin, J. A., Goldman, S. M., Korell, M., Marras, C., Bhudhikanok, G. S., Kasten, M., Chade, A. R., Comyns, K., Richards, M. B., Meng, C., Priestley, B., Fernandez, H. H., Cambi, F., Umbach, D. M., Blair, A., Sandler, D. P., & Langston, J. W. (2011). Rotenone, paraquat, and Parkinson’s disease. Environmental Health Perspectives, 119(6), 866–872.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Thiruchelvam, M., Brockel, B. J., Richfield, E. K., Baggs, R. B., & Cory-Slechta, D. A. (2000). Potentiated and preferential effects of combined paraquat and maneb on nigrostriatal dopamine systems: Environmental risk factors for Parkinson’s disease? Brain Research, 873(2), 225–234.

    CAS  PubMed  Google Scholar 

  • Thiruchelvam, M. J., Powers, J. M., Cory-Slechta, D. A., & Richfield, E. K. (2004). Risk factors for dopaminergic neuron loss in human alpha-synuclein transgenic mice. European Journal of Neuroscience, 19(4), 845–854.

    CAS  PubMed  Google Scholar 

  • Uversky, V. N., Li, J., & Fink, A. L. (2001). Pesticides directly accelerate the rate of alpha-synuclein fibril formation: A possible factor in Parkinson’s disease. FEBS Letters, 500(3), 105–108.

    CAS  PubMed  Google Scholar 

  • Uversky, V. N., Yamin, G., Munishkina, L. A., Karymov, M. A., Millett, I. S., Doniach, S., Lyubchenko, Y. L., & Fink, A. L. (2005). Effects of nitration on the structure and aggregation of alpha-synuclein. Brain Research. Molecular Brain Research, 134(1), 84–102.

    CAS  PubMed  Google Scholar 

  • Ved, R., Saha, S., Westlund, B., Perier, C., Burnam, L., Sluder, A., Hoener, M., Rodrigues, C. M., Alfonso, A., Steer, C., Liu, L., Przedborski, S., & Wolozin, B. (2005). Similar patterns of mitochondrial vulnerability and rescue induced by genetic modification of alpha-synuclein, parkin, and DJ-1 in Caenorhabditis elegans. Journal of Biological Chemistry, 280(52), 42655–42668.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Vogt, M., Bauer, M. K., Ferrari, D., & Schulze-Osthoff, K. (1998). Oxidative stress and hypoxia/reoxygenation trigger CD95 (APO-1/Fas) ligand expression in microglial cells. FEBS Letters, 429(1), 67–72.

    CAS  PubMed  Google Scholar 

  • Walls, K. C., Ghosh, A. P., Franklin, A. V., Klocke, B. J., Ballestas, M., Shacka, J. J., Zhang, J., & Roth, K. A. (2010). Lysosome dysfunction triggers Atg7-dependent neural apoptosis. Journal of Biological Chemistry, 285(14), 10497–10507.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang, C., Ko, H. S., Thomas, B., Tsang, F., Chew, K. C., Tay, S. P., Ho, M. W., Lim, T. M., Soong, T. W., Pletnikova, O., Troncoso, J., Dawson, V. L., Dawson, T. M., & Lim, K. L. (2005). Stress-induced alterations in parkin solubility promote parkin aggregation and compromise parkin’s protective function. Human Molecular Genetics, 14(24), 3885–3897.

    CAS  PubMed  Google Scholar 

  • Wang, A., Costello, S., Cockburn, M., Zhang, X., Bronstein, J., & Ritz, B. (2011). Parkinson’s disease risk from ambient exposure to pesticides. European Journal of Epidemiology, 26(7), 547–555.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wechsler, L. S., Checkoway, H., Franklin, G. M., & Costa, L. G. (1991). A pilot study of occupational and environmental risk factors for Parkinson’s disease. Neurotoxicology, 12(3), 387–392.

    CAS  PubMed  Google Scholar 

  • Whitworth, A. J., Wes, P. D., & Pallanck, L. J. (2006). Drosophila models pioneer a new approach to drug discovery for Parkinson’s disease. Drug Discovery Today, 11(3–4), 119–126.

    CAS  PubMed  Google Scholar 

  • Wirdefeldt, K., Adami, H. O., Cole, P., Trichopoulos, D., & Mandel, J. (2011). Epidemiology and etiology of Parkinson’s disease: A review of the evidence. European Journal of Epidemiology, 26(Suppl 1), S1–S58.

    PubMed  Google Scholar 

  • Wu, X. F., Block, M. L., Zhang, W., Qin, L., Wilson, B., Zhang, W. Q., Veronesi, B., & Hong, J. S. (2005). The role of microglia in paraquat-induced dopaminergic neurotoxicity. Antioxidants & Redox Signaling, 7(5–6), 654–661.

    CAS  Google Scholar 

  • Yanase, S., Yasuda, K., & Ishii, N. (2002). Adaptive responses to oxidative damage in three mutants of Caenorhabditis elegans (age-1, mev-1 and daf-16) that affect life span. Mechanisms of Ageing and Development, 123(12), 1579–1587.

    CAS  PubMed  Google Scholar 

  • Yang, W., & Tiffany-Castiglioni, E. (2008). Paraquat-induced apoptosis in human neuroblastoma SH-SY5Y cells: Involvement of p53 and mitochondria. Journal of Toxicology and Environmental Health. Part A, 71(4), 289–299.

    CAS  PubMed  Google Scholar 

  • Yang, W., Tiffany-Castiglioni, E., Koh, H. C., & Son, I. H. (2009). Paraquat activates the IRE1/ASK1/JNK cascade associated with apoptosis in human neuroblastoma SH-SY5Y cells. Toxicology Letters, 191(2–3), 203–210.

    CAS  PubMed  Google Scholar 

  • Yumino, K., Kawakami, I., Tamura, M., Hayashi, T., & Nakamura, M. (2002). Paraquat- and diquat-induced oxygen radical generation and lipid peroxidation in rat brain microsomes. Journal of Biochemistry, 131(4), 565–570.

    CAS  PubMed  Google Scholar 

  • Zaidi, A., Fernandes, D., Bean, J. L., & Michaelis, M. L. (2009). Effects of paraquat-induced oxidative stress on the neuronal plasma membrane Ca(2+)-ATPase. Free Radical Biology & Medicine, 47(10), 1507–1514.

    CAS  Google Scholar 

Download references

Acknowledgments

Mireia Niso-Santano was supported as a postdoctoral researcher by the University of Extremadura. Ruben Gómez-Sánchez was supported by a Spanish Ministerio de Educación predoctoral fellowship. Rosa A. González-Polo was supported by a “Miguel Servet” contract (Ministerio de Economia y Competitividad, ISCIII, Spain). Elisa Pizarro-Estrella was supported by a predoctoral contract from CIBERNED. Dr. González-Polo received research support from ISCIII [Ministerio de Economia y Competitividad, ISCIII, Spain (CP0800010, PI11/0040) and FUNDESALUD (PRIS11014)]. Dr. José M. Fuentes received research support from the Ministerio de Ciencia e Innovación, Spain (SAF2010-14993, PI12/022804), FUNDESALUD (PRIS11019), CIBERNED (CB06/05/004), and Consejería de Economía, Comercio e Innovación, Junta de Extremadura (GRU10054).

Author information

Authors and Affiliations

  1. Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Enfermería y TO, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Universidad de Extremadura, 10003, Cáceres, Spain

    Rosa A. González-Polo, José M. Bravo-San Pedro, Rubén Gómez-Sánchez, Elisa Pizarro-Estrella, Mireia Niso-Santano & José M. Fuentes

Authors
  1. Rosa A. González-Polo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. José M. Bravo-San Pedro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rubén Gómez-Sánchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elisa Pizarro-Estrella
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mireia Niso-Santano
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. José M. Fuentes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rosa A. González-Polo .

Editor information

Editors and Affiliations

  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, Tennessee, USA

    Richard M. Kostrzewa

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this entry

Cite this entry

González-Polo, R.A., Bravo-San Pedro, J.M., Gómez-Sánchez, R., Pizarro-Estrella, E., Niso-Santano, M., Fuentes, J.M. (2014). Links Between Paraquat and Parkinson’s Disease. In: Kostrzewa, R. (eds) Handbook of Neurotoxicity. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5836-4_4

Download citation

Publish with us

Policies and ethics

Search

Navigation