Abstract
Selective neurotoxins have the ability to exert their neurotoxic effects in some specific neuronal systems. In dopaminergic neurons, the selectivity of exogenous neurotoxins depends on their affinity to the dopamine transporter. However, dopamine and 3,4-L-dihydroxyphenylalanine (L-dopa) are synthesized in dopaminergic neurons and are likewise able to induce neurotoxicity. The possible molecular mechanisms involved in dopamine and L-dopa neurotoxicity in dopaminergic neurons are discussed. Dopamine seems to be neurotoxic in dopaminergic neurons by undergoing oxidation to aminochrome, which is the precursor to neuromelanin. However, aminochrome can be neurotoxic when it forms adducts with proteins such as alpha-synuclein, parkin, mitochondrial complexes I and III, actin, tubulin, and the dopamine transporter, or when aminochrome is one-electron reduced by flavoenzymes that use NADH, generating redox cycling with the concomitant depletion of energy and the formation of reactive oxygen species. L-dopa is also neurotoxic in cell cultures after oxidizing to a quinone species, but L-dopa seems to be a transient precursor of dopamine in that it is not able to induce neurotoxicity in vivo due to the efficient decarboxylation to dopamine catalyzed by amino acid decarboxylase. In fact, the only metabolite found in vivo is L-3-o-methyldopa, as detected in microdialysis experiments in animals treated with L-dopa. L-dopa is used in Parkinson’s disease treatment, and it is still questionable whether L-dopa accelerates the degeneration of remaining dopaminergic neurons. It seems that L-dopa itself does not accelerate dopaminergic neuron degeneration because L-dopa is efficiently converted to dopamine, both in the peripheral and the central nervous systems. However, L-dopa induces dyskinesias in approximately 40 % patients with 4–6 years of treatment, and although the mechanism for L-dopa-induced dyskinesias is very complex, the rapid oscillation of striatal dopamine during L-dopa treatment has been found to be required for the induction of dyskinesias. The remaining dopaminergic neurons convert L-dopa to dopamine and release dopamine to the striatum under regulated conditions, but the majority of dopamine release to the striatum is mediated by serotonergic neurons without regulation, resulting in dyskinesias.
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Abbreviations
- AADC:
-
Aromatic amino acid decarboxylase
- COMT:
-
Catechol ortho-methyltransferase
- DA:
-
Dopamine
- GST M2-2:
-
Glutathione S-transferase M2-2
- L-dopa:
-
L-dihydroxyphenylalanine
- MAO:
-
Monoamine oxidases
- TH:
-
Tyrosine hydroxylase
- VMAT-2:
-
Vesicular monoaminergic transporter-2
References
Ahlskog, J. E., & Muenter, M. D. (2001). Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Movement Disorders, 16, 448–458.
Arriagada, A., Paris, I., Matas MJ, S. d. l., Martinez-Alvarado, P., Cardenas, S., Castañeda, P., Graumann, R., Perez-Pastene, C., Olea-Azar, C., Couve, E., Herrero, M. T., Caviedes, P., & Segura-Aguilar, J. (2004). On the neurotoxicity of leukoaminochrome o-semiquinone radical derived of dopamine oxidation: Mitochondria damage, necrosis and hydroxyl radical formation. Neurobiology of Disease, 16, 468–477.
Asanuma, M., Miyazaki, I., Kikkawa, Y., Kimoto, N., Takeshima, M., Murakami, S., & Miyoshi, K. (2012). Cyclooxygenase-independent neuroprotective effects of aspirin against dopamine quinone-induced neurotoxicity. Neurochemical Research, 37, 1944–1951.
Baez, S., Linderson, Y., & Segura-Aguilar, J. (1994). Superoxide dismutase and catalase prevent the formation of reactive oxygen species during reduction of cyclized dopa ortho-quinone by DT-diaphorase. Chemico-Biological Interactions, 93, 103–116.
Baez, S., Linderson, Y., & Segura-Aguilar, J. (1995). Superoxide dismutase and catalase enhance autoxidation during one-electron reduction of aminochrome by NADPH-cytochrome P-450 reductase. Biochemical and Molecular Medicine, 54, 12–18.
Baez, S., Segura-Aguilar, J., Widersten, M., Johansson, A. S., & Mannervik, B. (1997). Glutathione transferases catalyse the detoxication of oxidized metabolites (o-quinones) of catecholamines and may serve as an antioxidant system preventing degenerative cellular processes. The Biochemical Journal, 324, 25–28.
Berthet, A., Bezard, E., Porras, G., Fasano, S., Barroso-Chinea, P., Dehay, B., Martinez, A., Thiolat, M. L., Nosten-Bertrand, M., Giros, B., Baufreton, J., Li, Q., Bloch, B., & Martin-Negrier, M. L. (2012). L-dopa impairs proteasome activity in parkinsonism through D1 dopamine receptor. The Journal of Neuroscience, 32, 681–691.
Braak, H., Ghebremedhin, E., Rüb, U., Bratzke, H., & Del Tredici, K. (2004). Stages in the development of Parkinson’s disease-related pathology. Cell and Tissue Research, 318, 121–134.
Cardenas, S. P., Perez-Pastene, C., Couve, E., & Segura-Aguilar, J. (2008). The DT-diaphorase prevents the aggregation of α-synuclein induced by aminochrome. Neurotoxicity Research, 13, 136.
Carstam, R., Brinck, C., Hindemith-Augustsson, A., Rorsman, H., & Rosengren, E. (1991). The neuromelanin of the human substantia nigra. Biochimica et Biophysica Acta, 1097, 152–160.
Cartier, E. A., Parra, L. A., Baust, T. B., Quiroz, M., Salazar, G., Faundez, V., Egaña, L., & Torres, G. E. (2010). A biochemical and functional protein complex involving dopamine synthesis and transport into synaptic vesicles. The Journal of Biological Chemistry, 151, 957–666.
Caudle, W. M., Richardson, J. R., Wang, M. Z., Taylor, T. N., Guillot, T. S., McCormack, A. L., Colebrooke, R. E., Di Monte, D. A., Emson, P. C., & Miller, G. W. (2007). Reduced vesicular storage of dopamine causes progressive nigrostriatal neurodegeneration. The Journal of Neuroscience, 27, 8138–8148.
Cheng, F. C., Kuo, J. S., Chia, L. G., & Dryhurst, G. (1996). Elevated 5-S-cysteinyldopamine/homovanillic acid ratio and reduced homovanillic acid in cerebrospinal fluid: Possible markers for and potential insights into the pathoetiology of Parkinson’s disease. Journal of Neural Transmission, 103, 433–446.
Cheshire, P. A., & Williams, D. R. (2012). Serotonergic involvement in levodopa-induced dyskinesias in Parkinson’s disease. Journal of Clinical Neuroscience, 19, 343–348.
Claffey, D. J., & Ruth, J. A. (2001). Amphetamine adducts of melanin intermediates demonstrated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Chemical Research in Toxicology, 14, 1339–1344.
Conway, K. A., Rochet, J. C., Bieganski, R. M., & Lansbury, P. T., Jr. (2001). Kinetic stabilization of the a-synuclein protofibril by a dopamine- a-synuclein adduct. Science, 294, 1346–1349.
Cuervo, A. M., Wong, E. S., & Martinez-Vicente, M. (2010). Protein degradation, aggregation, and misfolding. Movement Disorders, 25(Suppl 1), S49–S54.
Dagnino-Subiabre, A., Cassels, B. K., Baez, S., Johansson, A. S., Mannervik, B., & Segura-Aguilar, J. (2000). Glutathione transferase M2-2 catalyzes conjugation of dopamine and dopa o-quinones. Biochemical and Biophysical Research Communications, 274, 32–36.
Dehn, D. L., Claffey, D. J., Duncan, M. W., & Ruth, J. A. (2001). Nicotine and cotinine adducts of a melanin intermediate demonstrated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Chemical Research in Toxicology, 14, 275–279.
Díaz-Véliz, G., Paris, I., Mora, S., Raisman-Vozari, R., & Segura-Aguilar, J. (2008). Copper neurotoxicity in rat substantia nigra and striatum is dependent on DT-diaphorase inhibition. Chemical Research in Toxicology, 21, 1180–1185.
Fasano, M., Bergamasco, B., & Lopiano, L. (2006). Is neuromelanin changed in Parkinson’s disease? Investigations by magnetic spectroscopies. J. Neural Transm, 113, 769–774.
Foppoli, C., Coccia, R., Cini, C., & Rosei, M. A. (1997). Catecholamines oxidation by xanthine oxidase. Biochimica et Biophysica Acta, 1334, 200–206.
Fuentes, P., Paris, I., Nassif, M., Caviedes, P., & Segura-Aguilar, J. (2007). Inhibition of VMAT-2 and DT-diaphorase induce cell death in a substantia nigra-derived cell line–an experimental cell model for dopamine toxicity studies. Chemical Research in Toxicology, 20, 776–783.
Galzigna, L., De Iuliis, A., & Zanatta, L. (2000). Enzymatic dopamine peroxidation in substantia nigra of human brain. Clinica Chimica Acta, 300, 131–138.
Gerlach, M., Double, K. L., Ben-Shachar, D., Zecca, L., Youdim, M. B., & Riederer, P. (2003). Neuromelanin and its interaction with iron as a potential risk factor for dopaminergic neurodegeneration underlying Parkinson’s disease. Neurotoxicity Research, 5, 35–44.
Giménez-Xavier, P., Francisco, R., Santidrián, A. F., Gil, J., & Ambrosio, S. (2009). Effects of dopamine on LC3-II activation as a marker of autophagy in a neuroblastoma cell model. Neurotoxicology, 30, 658–665.
Gómez-Santos, C., Ferrer, I., Santidrián, A. F., Barrachina, M., Gil, J., & Ambrosio, S. (2003). Dopamine induces autophagic cell death and alpha-synuclein increase in human neuroblastoma SH-SY5Y cells. Journal of Neuroscience Research, 73, 341–350.
Graham, D. G., Tiffany, S. M., Bell, W. R., Jr., & Gutknecht, W. F. (1978). Autoxidation versus covalent binding of Autoxidation versus covalent binding of quinones as the mechanism of toxicity of dopamine, 6-hydroxydopamine, and related compounds toward C1300 neuroblastoma cells in vitro. Molecular Pharmacology, 14, 644–653.
Guillot, T. S., & Miller, G. W. (2009). Protective actions of the vesicular monoamine transporter 2 (VMAT2) in monoaminergic neurons. Molecular Neurobiology, 39, 149–170.
Hastings, T. G. (1995). Enzymatic oxidation of dopamine: The role of prostaglandin H synthase. Journal of Neurochemistry, 64, 919–924.
Hong, L., & Simon, J. D. (2007). Current understanding of the binding sites, capacity, affinity, and biological significance of metals in melanin. The Journal of Physical Chemistry. B, 111, 7938–4797.
Hoyt, K. R., Reynolds, I. J., & Hastings, T. G. (1997). Mechanisms of dopamine-induced cell death in cultured rat forebrain neurons: Interactions with and differences from glutamate-induced cell death. Experimental Neurology, 143, 269–281.
Jana, S., Sinha, M., Chanda, D., Roy, T., Banerjee, K., Munshi, S., Patro, B. S., & Chakrabarti, S. (2011). Mitochondrial dysfunction mediated by quinone oxidation products of dopamine: Implications in dopamine cytotoxicity and pathogenesis of Parkinson’s disease. Biochimica et Biophysica Acta, 1812, 663–673.
Jeon, S. M., Cheon, S. M., Bae, H. R., Kim, J. W., & Kim, S. U. (2010). Selective susceptibility of human dopaminergic neural stem cells to dopamine-induced apoptosis. Experimental Neurobiology, 19, 155–164.
Jiang, H., Ren, Y., Zhao, J., & Feng, J. (2004). Parkin protects human dopaminergic neuroblastoma cells against dopamine-induced apoptosis. Human Molecular Genetics, 13, 1745–1754. 15.
Jimenez, M., Garcia-Carmona, F., Garcia-Canovas, F., Iborra, J. L., Lozano, J. A., & Martinez, F. (1984). Chemical intermediates in dopamine oxidation by tyrosinase, and kinetic studies of the process. Archives of Biochemistry and Biophysics, 235, 438–448.
Junn, E., & Mouradian, M. M. (2001). Apoptotic signaling in dopamine-induced cell death: The role of oxidative stress, p38 mitogen-activated protein kinase, cytochrome c and caspases. Journal of Neurochemistry, 78, 374–383.
Keller, J. N., Huang, F. F., Dimayuga, E. R., & Maragos, W. F. (2000). Dopamine induces proteasome inhibition in neural PC12 cell line. Free Radical Biology & Medicine, 29, 1037–1042.
Kostrzewa, R. M., Kostrzewa, J. P., & Brus, R. (2002). Neuroprotective and neurotoxic roles of levodopa (L-dopa) in neurodegenerative disorders relating to Parkinson’s disease. Amino Acids, 23, 57–63.
Kubo, I., Nitoda, T., & Nihei, K. (2007). Effects of quercetin on mushroom tyrosinase and B16-F10 melanoma cells. Molecules, 12, 1045–1056.
Kuhn, D. M., & Arthur, R., Jr. (1998). Dopamine inactivates tryptophan hydroxylase and forms a redox-cycling quinoprotein: Possible endogenous toxin to serotonin neurons. The Journal of Neuroscience, 18, 7111–7117.
LaVoie, M. J., Ostaszewski, B. L., Weihofen, A., Schlossmacher, M. G., & Selkoe, D. J. (2005). Dopamine covalently modifies and functionally inactivates parkin. Nature Medicine, 11, 1159–1161.
Lee, F. J., Liu, F., Pristupa, Z. B., & Niznik, H. B. (2001a). Direct binding and functional coupling of alpha-synuclein to the dopamine transporters accelerate dopamine-induced apoptosis. The FASEB Journal B, 15, 916–926.
Lee, H. J., Kim, S. H., Kim, K. W., Um, J. H., Lee, H. W., Chung, B. S., & Kang, C. D. (2001b). Antiapoptotic role of NF-kappaB in the auto-oxidized dopamine-induced apoptosis of PC12 cells. Journal of Neurochemistry, 76, 602–609.
Liedhegner, E. A., Steller, K. M., & Mieyal, J. J. (2011). Levodopa activates apoptosis signaling kinase 1 (ASK1) and promotes apoptosis in a neuronal model: Implications for the treatment of Parkinson’s disease. Chemical Research in Toxicology, 24, 1644–1652.
Linert, W., Herlinger, E., Jameson, R. F., Kienzl, E., Jellinger, K., & Youdim, M. B. (1996). Dopamine, 6-hydroxydopamine, iron, and dioxygen–their mutual interactions and possible implication in the development of Parkinson’s disease. Biochimica et Biophysica Acta, 1316, 160–168.
Liu, Z., Zhang, J., Fei, J., & Guo, L. (2001). A novel mechanism of dopamine neurotoxicity involving the peripheral extracellular and the plasma membrane dopamine transporter. Neuroreport, 12, 3293–3297.
Lozano, J., Muñoz, P., Nore, B. F., Ledoux, S., & Segura-Aguilar, J. (2010). Stable expression of short interfering RNA for DT-diaphorase induces neurotoxicity. Chemical Research in Toxicology, 23, 1492–1496.
Luo, Y., Umegaki, H., Wang, X., Abe, R., & Roth, G. S. (1998). Dopamine induces apoptosis through an oxidation-involved SAPK/JNK activation pathway. The Journal of Biological Chemistry, 273, 3756–3764.
Marin, C., & Obeso, J. A. (2010). Catechol-O-methyltransferase inhibitors in preclinical models as adjuncts of L-dopa treatment. International Review of Neurobiology, 95, 191–205.
McNaught, K. S., Perl, D. P., Brownell, A. L., & Olanow, C. W. (2004). Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson’s disease. Annals of Neurology, 56, 149–162.
Meissner, W., Ravenscroft, P., Reese, R., Harnack, D., Morgenstern, R., Kupsch, A., Klitgaard, H., Bioulac, B., Gross, C. E., Bezard, E., & Boraud, T. (2006). Increased slow oscillatory activity in substantia nigra pars reticulata triggers abnormal involuntary movements in the 6-OHDA-lesioned rat in the presence of excessive extracellular striatal dopamine. Neurobiol, 22, 586–598. Epub 2006 Mar 10.
Melamed, E., Offen, D., Shirvan, A., Djaldetti, R., Barzilai, A., & Ziv, I. (1998). Levodopa toxicity and apoptosis. Annals of Neurology, 44, S149–S154.
Monastyrska, I., Rieter, E., Klionsky, D. J., & Reggiori, F. (2009). Multiple roles of the cytoskeleton in autophagy. Biological Reviews of the Cambridge Philosophical Society, 84, 431–448.
Moszczynska, A., Saleh, J., Zhang, H., Vukusic, B., Lee, F. J., & Liu, F. (2007). Parkin disrupts the alpha-synuclein/dopamine transporter interaction: Consequences toward dopamine-induced toxicity. Journal of Molecular Neuroscience, 32, 217–227.
Müller, T., & Muhlack, S. (2012). Cysteine decrease following acute Levodopa intake in patients with Parkinson’s disease. Neuroscience Letters, 521, 37–39.
Muñoz, P., Huenchuguala, S., Paris, I., Cuevas, C., Villa, M., Caviedes, P., Segura-Aguilar, J., & Tizabi, Y. (2012a). Protective effects of nicotine against aminochrome-induced toxicity in substantia nigra derived cells: Implications for Parkinson’s disease. Neurotoxicity Research, 22, 177–180.
Muñoz, P., Paris, I., Sanders, L. H., Greenamyre, J. T., & Segura-Aguilar, J. (2012b). Overexpression of VMAT-2 and DT-diaphorase protects substantia nigra-derived cells against aminochrome neurotoxicity. Biochimica et Biophysica Acta, 1822, 1125–1136.
Myöhänen, T. T., Schendzielorz, N., & Männistö, P. T. (2010). Distribution of catechol-O-methyltransferase (COMT) proteins and enzymatic activities in wild-type and soluble COMT deficient mice. Journal of Neurochemistry, 113, 1632–1643.
Naoi, M., Maruyama, W., Yi, H., Yamaoka, Y., Shamoto-Nagai, M., Akao, Y., Gerlach, M., Tanaka, M., & Riederer, P. (2008). Neuromelanin selectively induces apoptosis in dopaminergic SH-SY5Y cells by deglutathionylation in mitochondria: Involvement of the protein and melanin component. Journal of Neurochemistry, 105, 2489–2500.
Norris, E. H., Giasson, B. I., Hodara, R., Xu, S., Trojanowski, J. Q., Ischiropoulos, H., & Lee, V. M. (2005). Reversible inhibition of alpha-synuclein fibrillization by dopaminochrome – mediated conformational alterations. The Journal of Biological Chemistry, 280, 21212–21219.
Offen, D., Ziv, I., Panet, H., Wasserman, L., Stein, R., Melamed, E., & Barzilai, A. (1997). Dopamine-induced apoptosis is inhibited in PC12 cells expressing Bcl-2. Cellular and Molecular Neurobiology, 17, 289–304.
Okada, M., Nakao, R., Hosoi, R., Zhang, M. R., Fukumura, T., Suzuki, K., & Inoue, O. (2011). Microdialysis with radiometric monitoring of L-[β-11C]DOPA to assess dopaminergic metabolism: Effect of inhibitors of L-amino acid decarboxylase, monoamine oxidase, and catechol-O-methyltransferase on rat striatal dialysate. Journal of Cerebral Blood Flow and Metabolism, 31, 124–131.
Paris, I., Dagnino-Subiabre, A., Marcelain, K., Bennett, L. B., Caviedes, P., Caviedes, R., Olea-Azar, C., & Segura-Aguilar, J. (2001). Copper neurotoxicity is dependent on dopamine-mediated copper uptake and one-electron reduction of aminochrome in a rat substantia nigra neuronal cell line. Journal of Neurochemistry, 77, 519–529.
Paris, I., Martinez-Alvarado, P., Cardenas, S., Perez-Pastene, C., Graumann, R., Fuentes, P., Olea-Azar, C., Caviedes, P., & Segura-Aguilar, J. (2005a). Dopamine-dependent iron toxicity in cells derived from rat hypothalamus. Chemical Research in Toxicology, 18, 415–419.
Paris, I., Martinez-Alvarado, P., Perez-Pastene, C., Vieira, M. N., Olea-Azar, C., Raisman-Vozari, R., Cardenas, S., Graumann, R., Caviedes, P., & Segura-Aguilar, J. (2005b). Monoamine transporter inhibitors and norepinephrine reduce dopamine-dependent iron dependent iron toxicity in cells derived from the substantia nigra. Journal of Neurochemistry, 92, 1021–1032.
Paris, I., Perez-Pastene, C., Couve, E., Caviedes, P., Ledoux, S., & Segura-Aguilar, J. (2009). Copper dopamine complex induces mitochondrial autophagy preceding caspase-independent apoptotic cell death. The Journal of Biological Chemistry, 284, 13306–13315.
Paris, I., Perez-Pastene, C., Cardenas, S., Iturriaga-Vasquez, P., Muñoz, P., Couve, E., Caviedes, P., & Segura-Aguilar, J. (2010). Aminochrome induces disruption of actin, alpha-, and beta-tubulin cytoskeleton networks in substantia-nigra-derived cell line. Neurotoxicity Research, 18, 82–92.
Paris, I., Muñoz, P., Huenchuguala, S., Couve, E., Sanders, L. H., Greenamyre, J. T., Caviedes, P., & Segura-Aguilar, J. (2011). Autophagy protects against aminochrome-induced cell death in substantia nigra-derived cell line. Toxicological Sciences, 121, 376–388.
Park, H. H., Lee, K. Y., Kim, S. H., Lee, Y. J., & Koh, S. H. (2009). L-dopa-induced neurotoxicity is reduced by the activation of the PI3K signaling pathway. Toxicology, 265, 80–86. 30.
Pavese, N., Evans, A. H., Tai, Y. F., Hotton, G., Brooks, D. J., Lees, A. J., & Piccini, P. (2006). Clinical correlates of levodopa-induced dopamine release in Parkinson disease: A PET study. Neurology, 67, 1612–1617.
Prota, G. (1995). The chemistry of melanins and melanogenesis. Fortschritte der Chemie Organischer Naturstoffe, 64, 93–148.
Rosengren, E., Linder-Eliasson, E., & Carlsson, A. (1985). Detection of 5-S-cysteinyldopamine in human brain. Journal of Neural Transmission, 63, 247–253.
Sabens, E. A., Distler, A. M., & Mieyal, J. J. (2010). Levodopa deactivates enzymes that regulate thiol-disulfide homeostasis and promotes neuronal cell death: Implications for therapy of Parkinson’s disease. Biochemistry, 49, 2715–2724.
Saura, J., Luque, J. M., Cesura, A. M., Da Prada, M., Chan-Palay, V., Huber, G., Loffler, J., & Richards, J. G. (1994). Increased monoamine oxidase B activity in plaque-associated astrocytes of alzheimer brains revealed by quantitative enzyme radioautography. Neuroscience, 62, 15–30.
Schapira, A. H. (2011). Mitochondrial pathology in Parkinson’s disease. The Mount Sinai Journal of Medicine, 78, 872–881.
Schapira, A. H., & Jenner, P. (2011). Etiology and pathogenesis of Parkinson’s disease. Movement Disorders, 26, 1049–1055.
Segura-Aguilar, J. (1996). Peroxidase activity of liver microsomal vitamin D 25-hydroxylase and cytochrome P450 1A2 catalyzes 25-hydroxylation of vitamin D3 and oxidation of dopamine to aminochrome. Biochemical and Molecular Medicine, 58, 122–129.
Segura-Aguilar, J., & Lind, C. (1989). On the mechanism of Mn3+ induced neurotoxicity of dopamine: Prevention of quinone derived oxygen toxicity by DT-diaphorase and superoxide dismutase. Chemico-Biological Interactions, 72, 309–324.
Segura-Aguilar, J., Baez, S., Widersten, M., Welch, C. J., & Mannervik, B. (1997). Human class Mu glutathione transferases, in particular isoenzyme M2-2, catalyze detoxication of the dopamine metabolite aminochrome. The Journal of Biological Chemistry, 272, 5727–5731.
Segura-Aguilar, J., Metodiewa, D., & Welch, C. (1998). Metabolic activation of dopamine o-quinones to o-semiquinones by NADPH cytochrome P450 reductase may play an important role in oxidative stress and apoptotic effects. Biochimica et Biophysica Acta, 1381, 1–6.
Segura-Aguilar, J., Cardenas, S., Riveros, A., Fuentes-Bravo, P., Lozano, J., Graumann, R., Paris, I., Nassif, M., & Caviedes, P. (2006). DT-diaphorase prevents the formation of alpha-synuclein adducts with aminochrome. Soc Neurosci Abstr, 824, 17.
Shen, X. M., Xia, B., Wrona, M. Z., & Dryhurst, G. (1996). Synthesis, redox properties, in vivo formation, and neurobehavioral effects of N-acetylcysteinyl conjugates of dopamine: Possible metabolites of relevance to Parkinson’s disease. Chemical Research in Toxicology, 9, 1117–1126.
Shih, J. C., Grimsby, J., & Chen, K. (1997). Molecular biology of monoamine oxidase A and B: Their role in the degradation of serotonin. In H. G. Baumgarten & M. Gothert (Eds.), Handbook of experimental pharmacology, vol 129, Serotoninergic neurons and 5-HT receptors in the CNS (pp. 655–670). Berlin: Springer.
Simantov, R., Blinder, E., Ratovitski, T., Tauber, M., Gabbay, M., & Porat, S. (1996). Dopamine-induced apoptosis in human neuronal cells: Inhibition by nucleic acids antisense to the dopamine transporter. Neuroscience, 74, 39–50.
Stokes, A. H., Lewis, D. Y., Lash, L. H., Jerome, W. G., 3rd, Grant, K. W., Aschner, M., & Vrana, K. E. (2000). Dopamine toxicity in neuroblastoma cells: Role of glutathione depletion by L-BSO and apoptosis. Brain Research, 858, 1–8.
Strolin-Benedetti, M., Dostert, P., & Tipton, K. F. (1992). Developmental aspects of the monoamine-degrading enzyme monoamine oxidase. Developmental Pharmacology and Therapeutics, 18, 191–200.
Takeshima, M., Murata, M., Urasoe, N., Murakami, S., Miyazaki, I., Asanuma, M., & Kita, T. (2011). Protective effects of baicalein against excess L-dopa-induced dopamine quinone neurotoxicity. Neurological Research, 33, 1050–1056.
Tanaka, H., Kannari, K., Maeda, T., Tomiyama, M., Suda, T., & Matsunaga, M. (1999). Role of serotonergic neurons in L-dopa-derived extracellular dopamine in the striatum of 6-OHDA-lesioned rats. Neuroreport, 10, 631–634. 25.
Thompson, M., Capdevila, J. H., & Strobel, H. W. (2000). Recombinant cytochrome P450 2D18 metabolism of dopamine and arachidonic acid. The Journal of Pharmacology and Experimental Therapeutics, 294, 1120–1130.
Van Laar, V. S., Mishizen, A. J., Cascio, M., & Hastings, T. G. (2009). Proteomic identification of dopamine-conjugated proteins from isolated rat brain mitochondria and SH-SY5Y cells. Neurobiology of Disease, 34, 487–500.
Walkinshaw, G., & Waters, C. M. (1995). Induction of apoptosis in catecholaminergic PC12 cells by L-dopa. Implications for the treatment of Parkinson’s disease. The Journal of Clinical Investigation, 95, 2458–2464.
Westlund, K. N., Denney, R. M., Rose, R. M., & Abell, C. W. (1988). Localization of distinct monoamine oxidase A and monoamine oxidase B cell populations in human brainstem. Neuroscience, 25, 439–456.
Weyler, W., Hsu, Y. P., & Breakefield, X. O. (1990). Biochemistry and genetics of monoamine oxidase. Pharmacology and Therapeutics, 47, 391–417.
Whitehead, R. E., Ferrer, J. V., Javitch, J. A., & Justice, J. B. (2001). Reaction of oxidized dopamine with endogenous cysteine residues in the human dopamine transporter. Journal of Neurochemistry, 76, 1242–1251.
Xilouri, M., Vogiatzi, T., Vekrellis, K., Park, D., & Stefanis, L. (2009). Abberant alpha-synuclein confers toxicity to neurons in part through inhibition of chaperone-mediated autophagy. PLoS One, 4, e5515.
Xu, Y., Stokes, A. H., Roskoski, R., Jr., & Vrana, K. E. (1998). Dopamine, in the presence of tyrosinase, covalently modifies and inactivates tyrosine hydroxylase. Journal of Neuroscience Research, 54, 691–697.
Zafar, K. S., Siegel, D., & Ross, D. (2006). A potential role for cyclized quinones derived from dopamine, DOPA, and 3,4-dihydroxyphenylacetic acid in proteasomal inhibition. Molecular Pharmacology, 70, 1079–1086.
Zecca, L., Fariello, R., Riederer, P., Sulzer, D., Gatti, A., & Tampellini, D. (2002). The absolute concentration of nigral neuromelanin, assayed by a new sensitive method, increases throughout the life and is dramatically decreased in Parkinson’s disease. FEBS Letters, 510, 216–220.
Zhang, N. Y., Tang, Z., & Liu, C. W. (2008). Alpha-Synuclein protofibrils inhibit 26 S proteasome-mediated protein degradation: Understanding the cytotoxicity of protein protofibrils in neurodegenerative disease pathogenesis. The Journal of Biological Chemistry, 283, 20288–20298.
Zhang, W., Phillips, K., Wielgus, A. R., Liu, J., Albertini, A., Zucca, F. A., Faust, R., Qian, S. Y., Miller, D. S., Chignell, C. F., Wilson, B., Jackson-Lewis, V., Przedborski, S., Joset, D., Loike, J., Hong, J. S., Sulzer, D., & Zecca, L. (2011). Neuromelanin activates microglia and induces degeneration of dopaminergic neurons: Implications for progression of Parkinson’s disease. Neurotoxicity Research, 19, 63–72.
Ziv, I., Shirvan, A., Offen, D., Barzilai, A., & Melamed, E. (2001). Molecular biology of dopamine-induced apoptosis: Possible implications for Parkinson’s disease. Methods in Molecular Medicine, 62, 73–87.
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Segura-Aguilar, J., Ahumada-Castro, U., Paris, I. (2014). Dopamine and L-dopa as Selective Endogenous Neurotoxins. In: Kostrzewa, R. (eds) Handbook of Neurotoxicity. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5836-4_70
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DOI: https://doi.org/10.1007/978-1-4614-5836-4_70
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