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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
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.
Berry, C., La Vecchia, C., & Nicotera, P. (2010). Paraquat and Parkinson’s disease. Cell Death and Differentiation, 17(7), 1115–1125.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Fei, Q., & Ethell, D. W. (2008). Maneb potentiates paraquat neurotoxicity by inducing key Bcl-2 family members. Journal of Neurochemistry, 105(6), 2091–2097.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Grimm, S., & Brdiczka, D. (2007). The permeability transition pore in cell death. Apoptosis, 12(5), 841–855.
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.
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.
Haley, T. J. (1979). Review of the toxicology of paraquat (1,1′-dimethyl-4,4′-bipyridinium chloride). Clinical Toxicology, 14(1), 1–46.
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.
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.
Kamel, F., & Hoppin, J. A. (2004). Association of pesticide exposure with neurologic dysfunction and disease. Environmental Health Perspectives, 112(9), 950–958.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Menzies, F. M., Ravikumar, B., & Rubinsztein, D. C. (2006). Protective roles for induction of autophagy in multiple proteinopathies. Autophagy, 2(3), 224–225.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Olanow, C. W. (2007). The pathogenesis of cell death in Parkinson’s disease–2007. Movement Disorders, 22(Suppl 17), S335–S342.
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.
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.
Orth, M., & Tabrizi, S. J. (2003). Models of Parkinson’s disease. Movement Disorders, 18(7), 729–737.
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.
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.
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.
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.
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.
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.
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.
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.
Purser, D. A., & Rose, M. S. (1979). The toxicity and renal handling of paraquat in cynomolgus monkeys. Toxicology, 15(1), 31–41.
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.
Ravagnan, L., Roumier, T., & Kroemer, G. (2002). Mitochondria, the killer organelles and their weapons. Journal of Cellular Physiology, 192(2), 131–137.
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.
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.
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.
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.
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.
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.
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.
Seidenfeld, J. J., Sobonya, R. E., & Toyoshima, J. M. (1985). Recovery from paraquat pneumonitis. British Journal of Industrial Medicine, 42(3), 178–183.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
Corresponding author
Editor information
Editors and Affiliations
Rights 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
DOI: https://doi.org/10.1007/978-1-4614-5836-4_4
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-5835-7
Online ISBN: 978-1-4614-5836-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences