Intraneuronal dopamine-quinone synthesis: A review

David Sulzer1, Luigi Zecca1,2
1Department of Neuroscience, Columbia University, New York State Psychiatric Institute, New York, USA
2Institute of Advanced Biomedical Technologies, CNR, Segrate, Italy

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Baba, M., Nakajo, S., Tu, P., Tomita, T., Nakaya, K., Lee, V., Trojanowski, J. and Iwatsubo, T. (1998). Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson’s disease and dementia with Lewy bodies.Am. J. Pathol. 152, 879–884.

Bancher, C., Lassmann, H., Budka, H., Jellinger, K., Grundke-Iqbal, I., Iqbal, Kv Wiche, G., Seitelberger, F. and Wisniewski, H.M. (1989). An antigenic profile of Lewy bodies: immunocytochemical indication for protein phosphorylation and ubiquitination.J. Neuropathol. Exp. Neurol. 48, 81–93.

Barden, H. (1970). Relationship of golgi thiaminepyrosphosphatase and lysosomal acid phosphatase to neuromelanin and lipofusin in crebral neurons of the aging rhesus monkey.J. Neuropathol. Exp. Neurol. 29, 225–240.

Baumeister, W. and Lupas, A. (1997). The proteasome.Curr. Opinion Struct. Biol. 7, 273–278.

Ben-Shachar, D., Zuk, R. and Glinka, Y. (1995). Dopamine neurotoxicity: inhibition of mitochondrial respiration.J. Neurochem. 64, 718–723.

Bertrand, E., Lechowicz, W., Szpak, G.M. and Dymecki, J. (1997). Qualitative and quantitative analysis of locus coeruleus neurons in Parkinson’s disease.Folia Neuropathologica 35, 80–86.

Blarzino, C., Mosca, L., Foppoli, C., Coccia, R., De Marco, C. and Rosei, M.A. (1999). Lipoxygenase/H202-catalyzed oxidation of dihdroxyindoles: synthesis of melanin pigments and study of their antioxidant properties.Free Radio. Biol. Med. 26, 446–453.

Brion, J.P. and Couck, A.M. (1995). Cortical and brainstem-type Lewy bodies are immunoreactive for the cyclin-dependent kinase 5.Am. J. Pathol. 147, 1465–1476.

Bruns, D. and Jahn, R. (1995). Real-time measurement of transmitter release from single synaptic vesicles.Nature 377, 62–65.

Cadet, J.L., Sheng, P., Ali, S., Rothman, R., Carlson, E. and Epstein, C. (1994). Attenuation of methamphetamineinduced neurotoxicity in copper/zinc superoxide dismutase transgenic mice.J. Neurochem. 62, 380–383.

Carstam, R., Brinck, C, Hindemith-Augustsson, A., Rorsman, H. and Rosengren, E. (1991). The neuromelanin of the human substantia nigra.Biochim. Biophys. Acta 1097, 152–160.

Castellani, R., Smith, M.A., Richey, PL. and Perry, G. (1996). Glycoxidation and oxidative stress in Parkinson disease and diffuse Lewy body disease.Brain Res. 737, 195–200.

Ciolkowski, EX., Maness, K.M., Cahill, PS., Wightman, R.M., Evans, D.H., Fosset, B. and Amatore, C. (1994). Disproportionation during electrooxidation of catecholamines at carbon-fiber microelectrodes.Anal. Chem. 66, 3611–3617.

Conconi, M. and Friguet, B. (1997). Proteasome inactivation upon aging and on oxidation effect of HSP 90.Molec. Biol. Reports 24, 45–50.

Crippa, R., Wang, Q.J., Eisner, M., Moss, S.C, Zecca, L., Zschack, P. and Gog, T. (1996). Structure of human neuromelanin by X-Ray diffraction: comparison with synthetics.Pigment Cell. Res. 5, 72.

Cubells, J.F., Rayport, S., Rajendran, G. and Sulzer, D. (1994). Methamphetamine neurotoxicity involves vacuolation of endocytic organelles and dopamine-dependent intracellular oxidative stress.J. Neurosci. 14, 2260–2271.

D’Amato, R.J., Alexander, G.M., Schwartzman, R.J., Kitt, C.A., Price, D.L. and Snyder, S.H. (1987). Neuromelanin: a role in MPTP-induced neurotoxicity.Life Sci. 40, 705–712.

D’Amato, R.J., Lipman, Z.P and Snyder, S.H. (1986). Selectivity of the parkinsonian neurotoxin MPTP: toxic metabolite MPP+ binds to neuromelanin.Science 231, 987–989.

D’lschia, M., Costantini, C. and Prota, G. (1996). Lipofuscin like pigments by autoxidation of polyunsaturated fatty acids in the presence of amine neurotransmitters: the role of malondialdehyde.Biochim. Biophys. Acta 1290, 319–326.

D’lschia, M. and Prota, G. (1997). Biosynthesis, structure, and function of neuromelanin and its relation to Parkinson’s Disease: a critical update.Pigment Cell. Res. 10, 370–376.

Daveu, C, Servy, C, Dendane, M., Marin, P. and Ducrocq, C. (1997). Oxidation and nitration of catecholamines by nitrogen oxides derived from nitric oxide.Nitric Oxide 1, 234–243.

Duffy, RE. and Tennyson, V.M. (1965). Phase and electron microscopic observations of Lewy bodies and melanin granules in the substantia nigra and locus coeruleus in Parkinson’s disease.J. Neuropathol. Exp. Neurol. 24, 398–414.

El-Ayaan, U., Herlinger, E., Jameson, R.F. and Linert, W. (1997). Anaerobic oxidation of dopamine by iron(III).J. Chem. Soc, Dalton Trans. 1997, 2813–2818.

El-Ayaan, U., Jameson, R.F. and Linert, W. (1998). A kinetic study of the reaction between noradrenaline and iron(III): an example of parallel inner- and outer-sphere electron transfer.J. Chem. Soc, Dalton Trans. 1998, 1315–1319.

Fahn, S. and Cohen, G. (1992). The oxidant stress hypothesis in Parkinson’s disease: evidence supporting it.Ann. Neurol. 32, 804–812.

Fergusson, J., Landon, M., Lowe, J., Dawson, S.P., Layfield, R., Hanger, D.P. and Mayer, R.J. (1996). Pathological lesions of Alzheimer’s disease and dementia with Lewy bodies brains exhibit immunoreactivity to an ATPase that is a regulatory subunit of the 26S proteasome.Neurosci. Lett. 219, 167–170.

Figueiredo-Pereira, M.E., Yakushin, S. and Cohen, G. (1997). Accumulation of ubiquitinated proteins in mouse neuronal cells induced by oxidative stress.Molec. Biol. Reports 24, 35–38.

Foley, J.M. and Baxter, D. (1958). On the nature of pigment granules in the cell of the locus coeruleus and substantia nigra.J. Neuropathol. Exp. Neurol. 7, 586–598.

Foppoli, C, Coccia, R., Cini, C. and Rosei, M.A. (1997). Catecholamines oxidation by xanthine oxidase.Biochim. Biophys. Acta 1334, 200–206.

Fornstedt, B., Brun, A., Rosengren, E. and Carlsson, A. (1989). The apparent autoxidation rate of catechols in dopaminerich regions of human brains increases with degree of depigmentaion of substantia nigra.J. Neural. Trans. 1, 299–295.

Fukuda, T., Tanaka, J., Watabe, K., Numoto, R.T. and Minamitani, M. (1993). Immunohistochemistry of neuronal inclusions in the cerebral cortex and brain-stem in Lewy body disease.Acta Pathologica Japonica 43, 545–551.

Fumagalli, E, Gainetdinov, R.R., Wang, Y.-M., Valenzano, K.J., Miller, G.W. and Caron, M.G. (1999). Increased methamphetamine neurotoxicity in heterozygous vesicular monoamine transporter 2 knock-out mice.J. Neurosci. 19, 2424–2431.

Gai, W.P., Blumbergs, PC. and Blessing, W.W. (1996). Microtubule associated protein 5 is a component of Lewy bodies and Lewy neurites in the brainstem and forebrain regions affected in Parkinson’s disease.Acta Neuropathologica 91, 78–81.

Galvin, J.E., Lee, V.M., Baba, M., Mann, D.M., Dickson, D.W., Yamaguchi, H., Schmidt, M.L., Iwatsubo, T. and Trojanowski, J.Q. (1997). Monoclonal antibodies to purified cortical Lewy bodies recognize the mid size neurofilament subunit.Ann. Neurol. 42, 595–603.

Goldberg, A.L., Akopian, T.N., Kisselev, A.F, Lee, D.H. and Rohrwild, M. (1997). New insights into the mechanisms and importance of the proteasome in intracellular protein degradation.Biol. Chem. 378, 131–140.

Goldman, J.E., Yen, S.H., Chiu, EC. and Peress, N.S. (1983). Lewy bodies of Parkinson’s disease contain neurofilament antigens.Science 221, 1082–1084.

Gou, J.P. and Leterrier, J.F. (1995). Possible involvement of ubiquitination in neurofilament degradation.Biochem. Biophys. Res. Commun. 217, 529–538.

Graham, D.G. (1978). Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones.Molec. Pharmacol. 14, 633–643.

Graham, D.G. (1984). Catecholamine toxicity: a proposal for the molecular pathogenesis of manganese neurotoxicity and Parkinson’s disease.Neurotoxicol. 5, 83–96.

Gregori, L., Fuchs, C, Figueiredo-Pereira, M.E., Van Nostrand, W.E. and Goldgaber, D. (1995). Amyloid beta protein inhibits ubiquitin dependent protein degradation in vitro.J. Biol. Chem. 270, 19702–19708.

Grune, T, Reinheckel, T. and Davies, K.J. (1997). Degradation of oxidized proteins in mammalian cells.FASEB J. 11, 526–534.

Haavik, J. (1997). L-DOPA is a substrate for tyrosine hydroxylase.J. Neurochem. 69, 1720–1728.

Hastings, T.G. (1995). Enzymatic oxidation of dopamine: the role of prostoglandin H synthase.J. Neurochem. 64, 919–924.

Hastings, T.G. and Zigmond, M.J. (1994). Identification of catechol-protein conjugates in neostriatal slices incubated with [3H]dopamine: impact of ascorbic acid and glutathione.J. Neurochem. 63, 1126–1132.

Hayashida, K., Oyanagi, S., Mizutani, Y. and Yokochi, M. (1993). An early cytoplasmic change before Lewy body maturation: an ultrastructural study of the substantia nigra from an autopsy case of juvenile parkinsonism.Acta Neuropathologica 85, 445–448.

Hirsch, E.C., Mouatt, A., Faucheux, B., Bonnet, A.-M., Javoy-Agid, F, Graybiel, A.M. and Agid, Y. (1992). Dopamine, tremor, and Parkinson’s disease.Lancet 340, 125–126.

Holtzman, E. (1992). Membrane trafficking in neurons.Curr. Opin. Neurobiol. 2, 607–612.

Irizarry, M.C., Growdon, W., Gomez-Isla, T, Newell, K., George, J.M., Clayton, D.F and Hyman, B.T. (1998). Nigral and cortical Lewy bodies and dystrophic nigral neurites in Parkinson’s disease and cortical Lewy body disease contain alpha-synuclein immunoreactivity.J. Neuropathol. Exp. Neurol. 57, 334–337.

It, K., Ito, H., Tanaka, K. and Hirano, A. (1997). Immunocytochemical co-localization of the proteasome in ubiquitinated structures in neurodegenerative diseases and the elderly.J. Neuropathol. Exp. Neurol. 56, 125–131.

Ito, S., Kato, T. and Fujita, K. (1988). Covalent binding of catechols to proteins through the sulphydryl group.Biochem. Pharmacol. 37, 1707–1710.

Jenner, P. and Olanow, C.W. (1996). Oxidative stress and the pathogenesis of Parkinson’s disease.Neurology 47(6 Suppl. 3), S161-S170.

Johnson, R.G. (1988). Accumulation of biological amines into chromaffin granules: a model for hormone and neurotransmitter transport.Physiol. Rev. 68, 232–307.

Kato, S., Oda, M., Hayashi, H., Shimizu, T, Hayashi, M., Kawata, A. and Tanabe, H., (1995). Decrease of medullary catecholaminergic neurons in multiple system atrophy and Parkinson’s disease and their preservation in amyotrophic lateral sclerosis.J. Neurol. Sci. 132, 216–221.

Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y, Minoshima, S., Yokochi, M., Mizuno, Y. and Simizu, N. (1998). Mutations in theparkin gene cause autosomal recessive juvenile parkinsonism.Nature 392, 605–608.

Klegeris, A., Korkina, L.G. and Greenfield, S.A. (1995). Autoxidation of dopamine: a comparison of luminescent and spectrophotometric detection in basic solutions.Free Radic. Biol. Med. 18, 215–222.

Korytowski, W., Sarna, T., Kalyanaraman, B. and Sealy, R.C. (1987). Tyrosinase-catalyzed oxidation of dopa and related catechol(amine)s: a kinetic electron spin resonance investigation using spin-stabilization and spin label oximetry.Biochim. Biophys. Acta 924, 383–392.

Kruger, R., Kuhn, W., Muller, T., Woitalla, D., Graeber, M., Kosel, S., Przuntek, H., Epplen, J.T., Schols, L. and Riess, O. (1998). Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson’s disease.Nature Genetics 18, 106–108.

Larsen, C.N., Price, J.S. and Wilkinson, K.D. (1996). Substrate binding and catalysis by ubiquitin C-terminal hydrolases: identification of two active site residues.Biochem. 35, 6735–6744.

La Voie, M.J. and Hastings, T.G. (1999). Dopamine quinone formation and protein modification associated with the striatal neurotoxicity of methamphetamine: evidence against a role for extracellular dopamine.J. Neurosci. 19, 1484–1491.

Li, H. and Dryhurst, G. (1997). Irreversible inhibition of mitochondrial complex I by 7-(2-aminoethyD-3,4-dihydro-5-hydroxy-2H-l,4-benzothiazine-3-carboxylic acid (DHBT-1): a putative nigral endotoxin of relevance to Parkinson’s disease.J. Neurochem. 69, 1530–1541.

Lindquist, N.G., Larsson, B.S. and Lyden-Sokolowski, A. (1988). Autoradiography of [14C]paraquat or [14C]diquat in frogs and mice: accumulation in neuromelanin.Neurosci. Lett. 93, 1–6.

Liu, Y, Schweitzer, E.S., Nirenberg, M.J., Pickel, V.M., Evans, C.J. and Edwards, R.H. (1994). Preferential localization of a vesicular monoamine transporter to dense core vesicles in PC12 cells.J. Cell Biol. 127, 1419–1433.

Lloyd, R.V. (1995). Mechanism of the manganese-catalyzed autoxidation of dopamine.Chem. Res. Toxicol. 8, 111–116.

Lowe, J., Mayer, R.J. and Landon, M. (1993). Ubiquitin in neurodegenerative diseases.Brain Pathol. 3, 55–65.

Lowe, J., McDermott, H., Landon, M., Mayer, R.J. and Wilkinson, K.D. (1990). Ubiquitin carboxyl terminal hydrolase (PGP 9.5) is selectively present in ubiquitinated inclusion bodies characteristic of human neurodegenerative diseases.J. Pathol. 161, 153–160.

Marinho, C.R. and Manso, C.F. (1993). [O2 generation during neuromelanin synthesis. The action of manganese] in Portuguese.Acta Medica Portuguesa 6, 547–554.

Masaki, T., Ishiura, S., Sugita, H. and Kwak, S. (1994). Multicatalytic proteinase is associated with characteristic oval structures in cortical Lewy bodies: an immunocytochemical study with light and electron microscopy.J. Neurol. Sci. 122, 127–134.

Mather, K., Watts, F.Z., Carroll, M., Whitehead, P., Swash, M., Cairn, N. and Burke, J. (1993). Antibody to an abnormal protein in amyotrophic lateral sclerosis identifies Lewy body like inclusions in ALS and Lewy bodies in Parkinson’s disease.Neurosci. Lett. 160, 13–16.

Mattammal, M.B., Strong, R., Lakshmi, V.M., Chung, H.D. and Stephenson, A.H. (1995). Prostaglandin H synthetasemediated metabolism of dopamine: implication for Parkinson’s Disease.J. Neurochem. 64, 1645–1654.

Mayer, R.J., Tipler, C, Arnold, J., Laszlo, L., Al-Khedhairy, A., Lowe, J. and Landon, M. (1996). Endosome lysosomes, ubiquitin and neurodegeneration.Adv. Exp. Med. Biol. 389, 261–269.

McRitchie, D.A., Cartwright, H.R. and Halliday, G.M. (1997). Specific A10 dopaminergic nuclei in the midbrain degenerate in Parkinson’s disease.Exp. Neurol. 144, 202–213.

Mena, M.A., Khan, U., Togasaki, D.M., Sulzer, D., Epstein, C.J. and Przedborski, S. (1997). Effects of wild-type and mutated copper/zinc superoxide dismutase on neuronal survival and L-DOPA-induced toxicity in postnatal midbrain culture.J. Neurochem. 69, 21–33.

Merad-Boudia, M., Nicole, A., Santiard-Baron, D., Saille, C. and Ceballos-Picot, I. (1998). Mitochondrial impairment as an early event in the process of apoptosis induced by glutathione depletion in neuronal cells: relevance to Parkinson’s disease.Biochem. Pharmacol. 56, 645–655.

Michel, P.P. and Hefti, F. (1990). Toxicity of 6-hydroxydopamine and dopamine for dopaminergic neurons in culture.J. Neurosci. Res. 26, 428–435.

Miller, J.W., Selhub, J. and Joseph, J.A. (1996). Oxidative damage caused by free radicals produced during catecholamine autoxidation: protective effects of O-methylation and melatonin.Free Radic. Biol. Med. 21, 241–249.

Montine, T.J., Farris, D.B. and Graham, D.G. (1995). Covalent crosslinking of neurofilament proteins by oxidized catechols as a potential mechanism of Lewy body formation.J. Neuropathol. Exp. Neurol. 54, 311–319.

Mosca, L., Blarzino, C, Coccia, R., Foppoli, C. and Rosei, M.A. (1998). Melanins from tetrahydroisoquinolines: spectroscopic characteristics, scavenging activity and redox transfer properties.Free Radic. Biol. Med. 24, 161–167.

Mosca, L., Foppoli, C, Coccia, R. and Rosei, M.A. (1996). Pheomelanin production by the lipoxygenase-catalyzed oxidation of 5-S-cysteinyldopa and 5-S-cysteinyldopa-mine.Pigment Cell. Res. 9, 117–125.

Mouatt-Prigent, A., Karlsson, J.O., Agid, Y. and Hirsch, E.C. (1996). Increased M calpain expression in the mesencephalon of patients with Parkinson’s disease but not in other neurodegenerative disorders involving the mesencephalon: a role in nerve cell death?Neurosci. 73, 979–987.

Murphy Jr., G.M., Forno, L.S., Higgins, L., Scardina, J.M., Eng, L.F. and Cordell, B. (1994). Development of a monoclonal antibody specific for the COOH terminal of beta amyloid 1 42 and its immunohistochemical reactivity in Alzheimer’s disease and related disorders.Am. J. Pathol. 144, 1082–1088.

Nakamura, S., Kawamoto, Y, Nakano, S., Akiguchi, I. and Kimura, J. (1997). p35nck5a and cyclin-dependent kinase 5 colocalize in Lewy bodies of brains Parkinson’s disease.Acta Neuropathologica 94, 153–157.

Nakashima, S. and Ikuta, F. (1984). Tyrosine hydroxylase protein in Lewy bodies of parkinsonian and senile brains.J. Neurol. Sci. 66, 91–96.

Napolitano, A., Crescenzi, O., Pezzella, A. and Prota, G. (1995). Generation of the neurotoxin 6-hydroxydopamine by peroxidase /H2O2 oxidation of dopamine.J. Med. Chem. 38, 917–922.

Nappi, A.J. and Vass, E. (1998). Hydroxyl radical formation via iron-mediated Fenton chemistry is inhibited by methylated catechols.Biochim. Biophys. Acta 1425, 159–167.

Nishimura, M., Tomimoto, H., Suenaga, T., Nakamura, S., Namba, Y, Ikeda, K., Akiguchi, I. and Kumura, J. (1994). Synaptophysin and chromogranin A immunoreactivities of Lewy bodies in Parkinson’s disease brains.Brain Res. 634, 339–344.

Nishiyama, K., Murayama, S., Shimizu, J., Ohya, Y, Kwak, S., Asayama, K. and Kanazawa, I. (1995). Cu/Zn superoxide dismutase like immunoreactivity is present in Lewy bodies from Parkinson disease: a light and electron microscopic immunocytochemical study.Acta Neuropathologica 89, 471–474.

Palumbo, A., d’lschia, M., Misuraca, G., De Martino, L. and Prota, G. (1995). Iron- and peroxide-dependent conjugation of dopamine with cysteine: oxidative routes to the novel brain metabolite 5-S-cysteinyldopamine.Biochim. Biophys. Acta 1245, 255–261.

Pearse, A.G.E. (1985).Histochemistry: Theoretical and Applied, 4th edn., Vol. 2 (Edinburgh: Churchill Livingstone).

Pezzella, A., d’Ischia, M., Napolitano, A., Misuraca, G. and Prota, G. (1997). Iron-mediated generation of the neurotoxin 6-hydroxydopamine quinone by reaction of fatty acid hydroperoxides with dopamine: a possible contributory mechanism for neuronal degeneration in Parkinson’s disease.J. Med. Chem. 40, 2211–2216.

Pollanen, M.S., Bergeron, C. and Weyer, L. (1993). Deposition of detergent resistant neurofilaments into Lewy body fibrils.Brain Res. 603, 121–124.

Polymeropoulos, M.H., Lavedan, C, Leroy, E., Ide, S.E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., Stenroos, E.S., Chandrasekharappa, S., Athanassiadou, A., Papapetropoulos, T., Johnson, W.G., Lazzarini, A.M., Duvoisin, R.C., Di Iorio, G., Golbe, L.I. and Nussbaum, R.L. (1997). Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease.Science 276.

Pothos, E.N., Davila, V. and Sulzer, D. (1998). Presynaptic recording of quanta from midbrain dopamine neurons and modulation of the quantal size.J. Neurosci. 18, 4106–4118.

Przedborski, S., Kostic, V, Jackson-Lewis, V., Naini, A.B., Simonetti, S., Fahn, S., Carlson, E., Epstein, C.J. and Cadet, J.L. (1992). Transgenic mice with increased Cu/Znsuperoxide dismutase activity are resistant to N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine-induced neurotoxicity.J. Neurosci. 12, 1658–1667.

Ratan, R.R., Lee, P.J. and Baraban, J.M. (1996). Serum deprivation inhibits glutathione depletion-induced death in embryonic cortical neurons: evidence against oxidative stress as a final common mediator of neuronal apoptosis.Neurochem. Int. 29, 153–157.

Rosei, M.A., Blarzino, C, Coccia, R., Foppoli, C, Mosca, L. and Cini, C. (1998a). Production of melanin pigments by cytochrome c/H2O2 system.Int. J. Biochem. Cell Biol. 30, 457–463.

Rosei, M.A., Foppoli, C, Wang, X.T., Coccia, R. and Mateescu, M.A. (1998b). Production of melanins by ceruloplasmin.Pigment Cell Res. 11, 98–102.

Rosei, M.A., Blarzino, C, Foppoli, C, Mosca, L. and Coccia, R. (1994). Lipoxygenase-catalyzed oxidation of catecholamines.Biochem. Biophys. Res. Commun. 200, 344–350.

Rosenberg, P.A. (1988). Catecholamine toxicity in cerebral cortex in dissociated cell culture.J. Neurosci. 8, 2887–2894.

Rosengren, E.E., Linder-Eliasson, and Carlsoon, A. (1985). Detection of 5-S-cysteinyldopamine in human brain.J. Neural. Trans. 63, 247–253.

Sanchez-Ferrer, A., Rodriguez-Lopez, J.N., Garcia-Canovas, F. and Garcia-Carmona, F (1995). Tyrosinase: a review of its mechanism.Biochem. Biophys. Acta 1247, 1–11.

Seiden, L.S., Sabol, K.E. and Ricaurte, G.A. (1993). Amphetamine: Effects on catecholamine systems and behavior.Ann. Rev. Pharmacol. Toxicol. 32, 639–677.

Shen, X.M. and Dryhurst, G. (1998). Iron- and manganesecatalyzed autoxidation of dopamine in the presence of L-cysteine: possible insights into iron- and manganesemediated dopaminergic neurotoxicity.Chem. Res. Toxicol. 11, 824–837.

Shen, X.M., Zhang, F. and Dryhurst, G. (1997). Oxidation of dopamine in the presence of cysteine: characterization of new toxic products.Chem. Res. Toxicol. 10, 147–155.

Shimohama, S., Perry, G., Richey, P., Takenawa, T, Whitehouse, P.J., Miyoshi, K., Suenaga, T., Matsumoto, S., Nishimura, M. and Kimura, J. (1993). Abnormal accumulation of phospholipase C delta in filamentous inclusions of human neurodegenerative diseases.Neurosci. Lett. 162, 183–186.

Simantov, R., Blinder, E., Ratovitski, T., Tauber, M., Gabbay, M. and Porat, S. (1996). Dopamine-induced apoptosis in human neuronal cells: inhibition by nucleic acids antisense to the dopamine transporter.Neurosci. 74, 39–50.

Smythies, J. (1996). On the function of neuromelanin.Peoc. R Soc. Lond. B 263, 487–489.

Spillantini, M.G., Schmidt, M.L., Lee, V.M.Y., Trojanowski, J.Q., Jakes, R. and Goedert, M. (1997). Alpha-synuclein in Lewy bodies.Nature 388, 839–840.

Spina, M.B., Squinto, S.P., Miller, J., Lindsay, R.M. and Hyman, C. (1992). Brain-derived neurotrophic factor protects dopamine neurons against 6-hydroxydopamine and N-methyl-4-phenylpyridinium ion toxicity: involvement of the glutathione system.J. Neurochem. 59, 99–106.

Stokes, A.H., Brown, B.G., Lee, C.K., Doolitle, D.J. and Vrana, K.E. (1996). Tyrosinase enhances the covalent modificiation of DNA by dopamine.Mol. Brain Res. 42, 167–170.

Stokes, A.H., Hastings, T.G. and Vrana, K.E. (1999). Cytotoxic and genotoxic potential of dopamine.J. Neurosci. Res. 55, 659–665.

Sulzer, D., Chen, T.K., Lau, Y.Y., Kristensen, H., Rayport, S. and Ewing, A. (1995). Amphetamine redistributes dopamine from synaptic vesicles to the cytosol and promotes reverse transport.J. Neurosci. 15, 4102–4108.

Sulzer, D. and Rayport, S. (1990). Amphetamine and other psychostimulants reduce pH gradients in midbrain dopaminergic neurons and chromaffin granules: a mechanism of action.Neuron. 5, 797–808.

Takeda, A., Mallory, M., Sundsmo, M., Honer, W., Hansen, L. and Masliah, E. (1998). Abnormal accumulation of NACP/ alpha-synuclein in neurodegenerative disorders.Am. J. Pathol. 152, 367–372.

Tief, K., Schmidt, A. and Beerman, F. (1998). New evidence for presence of tyrosinase in substantia nigra, forebrain, and midbrain.Molec. Brain Res. 53, 307–310.

van Leeuwen, F.W., de Kleijn, D.P., van den Hurk, H.H., Neubauer, A., Sonnemans, M.A., Sluijs, J.A., Koycu, S., Ramdjielal, R.D.J., Salehi, A., Martens, G.J.M., Grosveld, EG., Peter, J., Burbach, H. and Hoi, E.M. (1998). Frameshift mutants of beta amyloid precursor protein and ubiquitin-B in Alzheimer’s and Down patients.Science 279, 242–247.

Velez-Pardo, C, Del Rio, M.J., Ebinger, G. and Vauquelin, G. (1998). Monoamine and iron-related toxicity: from ‘serotonin-binding proteins’ to lipid peroxidation and apoptosis in PC12 cells.Gen. Pharmacol. 31, 19–24.

Velez-Pardo, C, Jimenez Del Rio, M., Verschueren, H., Ebinger, G. and Vauquelin, G. (1997). Dopamine and iron induce apoptosis in PC12 cells.Pharmacol. Toxicol. 80, 76–84.

Wakabayashi, K., Matsumoto, K., Takayama, K., Yoshimoto, M. and Takahashi, H. (1997). NACP, a presynaptic protein, immunoreactivity in Lewy bodies in Parkinson’s disease.Neurosci. Lett. 239, 45–48.

Wakamatsu, K., Ito, S. and Nagatsu, T. (1991). Cysteinyl-dopamine is not incorporated into neuromelanin.Neurosci. Lett. 131, 57–60.

Walkinshaw, G. and Waters, CM. (1995). Induction of apoptosis in catecholaminergic PC12 cells by L-DOPA. Implications for the treatment of Parkinson’s disease.J. Clinic. Inv. 95, 2458–2464.

Welch, W.J. and Gambetti, P. (1998). Chaperoning brain diseases.Nature 392, 23–24.

Xu, Y., Stokes, A.H., Freeman, W.M., Kumer, S.C., Vogt, B.A. and Vrana, K.E. (1997). Tyrosinase mRNA is expressed in human substantia nigra.Mol. Brain Res. 45, 159–162.

Yamada, T. (1995). Further observations on MxA positive Lewy bodies in Parkinson’s disease brain tissues.Neurosci. Lett. 195, 41–44.

Youdim, M.B. and Riederer, P. (1993). The role of iron in senescence of dopaminergic neurons in Parkinson’s disease.J. Neural. Trans. 40, 57–67.

Zecca, L., Parati, E., Mecacci, C. and Seraglia, R. (1992). The chemical characterization of melanin contained in substantia nigra of human brain.Biochim. Biophys. Acta 1138, 6–10.

Zecca, L., Pietra, R., Goj, C, Mecacci, C, Radice, D. and Sabbioni, E. (1994). Iron and other metals in neuromel-anin, substantia nigra, and putamen of human brain.J. Neurochem. 62, 1097–101.

Zecca, L., Shima, T., Stroppolo, A., Goj, C., Battiston, G.A., Gerbasi, R., Sarna, T. and Swartz, H.M. (1996). Interaction of neuromelanin and iron in substantia nigra and other areas of human brain.Neurosci. 73, 407–415.

Zhang, F. and Dryhurst, G. (1994). Effects of 1-cysteine on the oxidation chemistry of dopamine: new reaction pathways of potential relevance to idiopathic Parkinson’s Disease.J. Med. Chem. 37, 1084–1098.