Abstract
The fact that glutamate, dopamine, iron and reactive oxygen species are potentially individually highly neurotoxic molecules is well known. The purpose of this review is to examine the less well known complex ways in which their normal biological, as well as their neurotoxic activity, are interconnected in relation to fundamental neuronal functions. These functions include synaptic plasticity (formation and removal of synapses), endocytosis-based recycling of receptors for neurotransmitters and neuromodulators, the role of the redox balance between reactive oxygen species and antioxidants in synaptic function, and the possible role of iron-catecholamine complexes in antioxidant protection and intraneuronal iron transport. These systems are closely involved in several diseases of the nervous system including Parkinson’s disease, schizophrenia and Alzheimer’s disease. In all these oxidative stress and a failure of antioxidant defenses are involved. In the former two the neurotoxicity of catecholaminergic o-quinones is important. In the latter excessive oxidation of neuronal membranes and excessive endocytosis and receptor recycling may be an important factor.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Abdalla, D.S.P., Monteiro, H.P., Oliveira, J.A.C. and Bechara, E.J.H. (1986) Activities of superoxide dismutase and glutathione peroxidase in schizophrenic and manic depressive patients.Clin. Chem. 32, 805–807.
Antun, F.T., Burnett, G.B., Cooper, A.J., Daly, R.J., Smythies, J.R. and Zealley, A.K. (1971) The effects of L-methionine (without MAOI) in schizophrenia.J. Psychiatr. Res. 8, 63–71.
Beaudet, A., Stroh, X, Choi-Jackson, A., Sarrett, J., Mazella, J., Vincent, J.-P. and Kreinkamp, H.-L. (1998) Internalization of somatostatin via SST5: confocal and electron microscope studies.Abst. Soc. Neurosci. 24, 592.
Ben-Shacher, D., Eschel, G., Riederer, P. and Youdim, M.B. (1992) Role of iron and iron chelation in dopaminergic-induced neurodegeneration: implications for Parkinson’s disease.Ann. Neurol. 32, S105-S110.
Ben-Shachar, D., Zuk, R. and Glinka, Y. (1995) Dopamine neurotoxicity: inhibition of mitochondrial respiration.J. Neurochem.,64, 718–723.
Berman, S.B. and Hastings, T.G. (1997) Inhibition of glutamate transport in synaptosomes by dopamine oxidation and reactive oxygen species.J. Neurochem. 69, 1185–1195.
Blake, D.R., Winyard, P., Lunec, J., Williams, A., Good, P.A., Crewes, S.J., Gutteridge, J.M.C., Rowley, D., Halliwell, B., Cornish, A. and Hider, R.C. (1985) Cellular and ocular toxicity induced by desferrioxamine.Quart. J. Med. 56, 345–355.
Boudin, H., Schonbrunn, A., Vincent, J.P. and Beaudet, A. (1998) Regulation of the distribution and expression of somatostatin SST2A receptors by somatostatin in rat brain.Abst. Soc. Neurosci. 24, 591.
Bradbury, M.W.B. (1997) Transport of iron in the blood-brain-cerebrospinal fluid system.J. Neurochem. 69, 443–454.
Bretscher, M.S. and Aguado-Velasco, C. (1998) Membrane traffic during cell locomotion.Curr. Op. Cell Biol. 10, 537–541.
Breuer, W., Epsztejn, S. and Cabantchik, Z.L. (1995) Iron acquired from transferrin by K562 cells is delivered into a cytoplasmic pool of chelatable iron (II).J. Biol. Chem. 270, 24, 209–24, 215.
Breuer, W., Greenberg, E. and Cabantchik, Z.I. (1997) Newly delivered transferrin iron and oxidative cell injury.FEBS Lett. 403, 213–219.
Buckman, T.D., Kling, A.S., Eiduson, S., Sutphin, M.S. and Steinberg, A. (1987) Glutathione peroxidase and CT scan abnormalities in schizophrenia.Biol. Psychiatr. 22, 1349–1356.
Buckman, T.D., Kling, A., Sutphin, M.S., Steinberg, A. and Eiduson, S. (1990) Platelet glutathione peroxidase and monoamine oxidase activity in schizophrenics with CT scan abnormalities: relation to psychosocial variables.Psychiat. Res. 31, 1–14.
Cadet, J.L. and Kahler, L.A. (1994) Free radical mechanisms in schizophrenia and tardive dyskinesia.Neurosci. Biobehav. Rev. 18, 457–467.
Cammack, J., Ghasemzadeh, B. and Adams, R.N. (1991) The pharmacological profile of glutamate-evoked ascorbic acid efflux measured byin vivo electrochemistry.Brain Res. 565, 17–22.
Cao, T.T., Mays, R.W. and von Zastrow, M. (1998) Regulated endocytosis of G-protein-coupled receptors by a biochemically and functionally distinct subpopulation of clathrin-coated pits.J. Biol. Chan. 273, 24,592–24,602.
Carlsson, A., Waters, N. and Hansson, L.O. (1994) Neurotransmitter aberrations in schizophrenia: new findings. In: R. Fog, J. Gerlach and R. Hemmingsen (Eds.),Schizophrenia. An Integrated View. (Copenhagen, Munksgard).
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, P.L. and Perry, G. (1996) Glycoxidation and oxidative stress in Parkinson’s disease and diffuse Lewy body disease.Brain Res. 737, 195–200.
Cataldo, A.M., Barnett, J.L., Pieroni, C. and Nixon, R.A. (1997) Increased neuronal endocytosis and protease delivery to early endosomes in sporadic Alzheimer’s disease: neuro-pathologic evidence of increased beta-amyloidgenesis.J. Neurosci. 17, 6142–6151.
Cheng, F.-C, Kuo, J.-S., Chia, L.-G. and 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 patho-biology of Parkinson’s disease.J. Neur. Transmission. 103, 433–446.
Chiueh, C.C. and Rauhala, P. (1998) Free radicals and MPTP-induced selective destruction of substantia nigra compacta neurons.Adv. Pharmacol. 42, 796–800.
Coscia, C.J., Ignatova, E.G. and Belcheva, M.M. (1998) Receptor endocytosis is required for opioid stimulation of mitogen-activated protein (MAP) kinase.Abst. Soc. Neurosci. 24, 2054.
Coulanges, V., Andre, P., Ziegler, O., Buchheit, L. and Vidon, D.J.-M. (1997) Utilization of iron-catecholamine complexes involving ferric reductase activity.Infect. Immun. 65, 2778–2785.
Cuenod, M., Do, K.Q., Lauer, C.J. and Hulsboer, F. (1997) Could a glutathione model integrate both dopamine and glutamate hypothesis of schizophrenia?Biol. Psychiat. 42, 287S.
Dumartin, B., Caille, I., Gonon, F. and Bloch, B. (1998) Internalization of Dl dopamine receptor in striatal neuronsin vivo as evidence of activation by dopamine agonists.J. Neurosci. 18, 1650–1661.
Ferguson, S.S.G., Barak, L.S., Zhang, J., Laporte, S., Delia Rocco, G. and Caron, M.G. (1998) Formation, trafficking and dissociation of the /32- adrenergic receptor/ /3-arrestin endocytic complex.Abst. Soc. Neurosci. 24, 598.
Fuxe, K., Jansson, A., Tinner, B., Razanin, H., Wang, F.-H., Schött, PA., Agnati, L.F. and ögren, S.O. (1998) Internalization of exogenous ventricular galinin (1-29) into discrete nerve cell populations of the dorsal hippocampus of the rat.Abst. Soc. Neurosci. 24, 2052.
Gai, W.P., Geffen, L.B., Denoroy, L. and Blessing, W.W. (1993) Loss of CI and C3 epinephrine-synthesizing neurons in the medulla oblongata in Parkinson’s disease.Ann. Neurol. 33, 357–367.
Gozlan, H. and Ben-Ari, Y. (1995) NMDA receptor redox sites: are they targets for selective neuronal protection?TI Pharm. Sci. 16, 368–374
Grimes, M.L., Zhou, J., Beattie, E.C., Yuen, E.C., Hall, D.E., Valletta, J.S., Topp, K.S., LaVail, J.H., Bunnett, N.W. and Mobley, W.C. (1996) Endocytosis of activated TrkA: evidence that nerve growth factor induces formation of signalling endosomes.J. Neurosci. 16, 7950–7964.
Grof, S. (1963) Clinical and experimental study of central effects of adrenochrome.J. Neuropsychiatr. 5, 33–50.
Griinewald, R.A. (1993) Ascorbic acid in the brain.Brain Research Reviews 18, 123–133.
Hevroni, D., Rattner, A., Bundman, M., Lederfein, D., Gabarah, A., Mangelus, M., Silverman, M.A., Kedah, H., Noar, C, Kornuc, M., Hanoch, T, Seger, R., Theill, L.E., Nederi, E., Richter-Levin, G. and Cutri, Y. (1998) Hippo-campal plasticity involves extensive gene induction and multiple cellular mechanisms.J. Mol. Neurosci. 10, 76–98.
Hipkiss, A.R., Preston, J.E., Himswoth, D.T.M., Worthington, V.C. and Abbot, N.J. (1997) Protective effects of carnosine against malondialdehyde-induced toxicity towards rat brain endothelial cells.Neurosci. Lett. 238, 135–138.
Hipkiss, A.R. (1998) Carnosine, a protective, anti-ageing peptide?Intern. J. Biochem. Cell Biol. 30, 863–868.
Hirasawa, A., Awaji, T, Sugawara, X, Tsujimoto, A. and Tsijumoto, G. (1998) Differential mechanism for the cell surface sorting and agonist-promoted internalization of the alpha lB-adenoceptor.Brit. J. Pharmacol. 124, 55–62.
Hoffer, A., Osmond, H. and Smythies, J.R. (1954) Schizophrenia. A new approach. Part II.J. Ment. Sci. 100, 29–45.
Itoh, K., Weis, S., Mehraein, P. and Muller-Hocker, J. (1996) Cytochrome c oxidase deficits of the human substantia nigra in normal aging.Neurobiol. Aging 17, 843–841.
Jacobs, A. (1977) Low molecular weight intracellular iron transport compounds.Blood 50, 433–439.
Jahn, R. (1998) Synaptic transmission: two players team up for a new tune.Curr. Biol. 8, R856-R858.
Jans, D.A. and Hassan, G. (1998) Nuclear targeting by growth factors, cytokines, and their receptors: a role in signaling?Bioessays 20, 400–411.
Jenner, P. and Olanow, C.W. (1998) Understanding cell death in Parkinson’s disease.Ann. Neurol. 44S1, S77-S84.
Jordan, B., Cvejic, S. and Devi, L. (1998) Kappa opioid receptor regulation by endocytosis and dimerization.Abst. Soc. Neurosci. 24, 1095.
Kang, M.Y., Tsuchiya, M., Packer, L. and Manabe, M. (1998)In vitro study on the antioxidant potential of various drugs used in the preoperative period.Acta Anaesthesiologica Scandinavica 42, 4–12.
Koenig, J.A. and Edwardson, J.M. (1997) Endocytosis and recycling of G protein-coupled receptors.TI Pharmacol. Sci. 18, 276–287.
Liang, C.T. and Sacktor, B. (1978) The stimulation by catecholamines of guanylate cyclase activity in a cell-free system.J. Cyclic Nucleotide Res. 4, 97–111.
Lieb, K, Andrae, J., Reisert, I. and Pilgrim, C. (1995) Neurotoxicity of dopamine and protective effects of the NMDA receptor antagonist AP-5 differ between male and female dopaminergic neurons.Exp. Neurol. 134, 222–229.
Liu, J. and Mori, A. (1993) Monoamine metabolism provides an antioxidant defense in the brain against oxidant- and free radical-induced damage.Arch. Biochem. Biophys. 302, 118–127.
Liu, M.-T., Roche, K.W., Wenthold, R.J. and Kirchgessner, A. (1998) Reflex-evoked internalization of metabotropic gluta-mate receptors and expression of pCREB imimmoreactivity in enteric neurons.Abst. Soc. Neurosci. 24, 1273.
Mahadik, S.P. and Mukherjee, S. (1996) Free radical pathology and antioxidant defense in schizophrenia: a review.Schiz. Res. 19, 1–17.
Mahadik, S.P., Mukherjee, S., Scheaffer, R., Correnti, E.E. and Mahadik, J.S. (1998) Elevated plasma lipid peroxides at the onset of nonaffective psychosis.Biol. Psychiat. 43, 674–679.
Marder, K., Logroscino, G., Tang, M.X., Graziano, J., Cote, L., Louis, E., Alfano, B., Mejia, H., Slavkovich, V. and Mayeux, R. (1998) Systemic iron metabolism and mortality from Parkinson’s disease.Neurology 50, 1138–1140.
Mattammal, M.B., Strong, R., Lakshmi, V.M., Chung, H.D. and Stephenson, A.H. (1995) Prostaglandin H synthase-mediated metabolism of dopamine: implication for Parkinson’s disease.J. Neurochem. 64, 1645–1654.
McCreadie, R.G., MacDonald, E., Wiles, D., Campbell, G. and Paterson, J.R. (1995) The Nithsdale Schizophrenia Surveys. XIV. Plasma lipid peroxide and serum vitamin E levels in patients with and without tardive dyskinesia, and in normal subjects.Brit. J. Psychiat. 167, 610–617.
Melamed, Y., Sirota, P., Dicker, D.R. and Fishman, P. (1998) Superoxide anion production by neutrophils derived from peripheral blood of schizophrenic patients.Psychiatr. Res. 77, 29–34.
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 apotosis 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.
Milby, K.H., Mefford, I.N., Chey, W. and Adams, R.N. (1981)In vitro andin vivo depolarization coupled efflux of ascorbic acid in rat brain preparations.Br. Res. Bull. 7, 237–242.
Moos, T. and Morgan, E.H. (1998) Evidence for low molecular weight non-transferrin-bound iron in rat brain and cerebrospinal fluid.J. Neurosci. Res. 54, 486–494.
Mukherjee, S., Ghosh, R.N. and Maxfield, F.R. (1997) Endocytosis.Physiol. Rev. 77, 759–803.
Murakami, A., Tatsuno, T., Kimura, X, Noguchi, H. and Nakamura, M. (1993) Regulation of nerve growth factor secretion in L-M cells by catechol derivatives.Neurosci. Res. 17, 71–75.
Muthane, U., Yasha, T.C. and Shankar, S.K. (1998) Low numbers and no loss of melanized nigral neurons with increasing age in normal human brains in India.Ann. Neurol. 43, 283–287.
Nakamura, K, Wang, W. and Kang, U.J. (1997) The role of glutathione in dopaminergic neuronal survival.J. Neurochem. 69, 1850–1858.
Neve, R.L., Coopersmith, R., McPhie, D.L., Santeufemio, C, Pratt, K.G., Murphy, C.J. and Lynn, S.D. (1998) The neuronal growth-associated protein GAP-43 interacts with rabaptin-5 and participates in endocytosis.J. Neurosci. 18, 7757–7767.
O’Brien, P.J. (1998) Personal communication.
Odh, G., Carstam, R., Paulson, J., Wittbjer, A., Rosengren, E. and Rorsman, H. (1994) Neuromelanin of the human substantia nigra: a mixed type melanin.J. Neurochem. 62, 2030–2036.
Ohmori, T., Abekawa, T. and Koyama, T. (1996) The role of glutamate in behavioral and neurotoxic effects of metham-phetamine.Neurochem. Int. 29, 301–307.
Ollinger, K. and Brunk, U.T. (1995) Cellular injury induced by oxidative stress is mediated through lysosomal damage.Free Rad. Biol. Med. 19, 565–574.
Pearce, R.K.B., Owen, A., Daniel, S., Jenner, P. and Marsden, CD. (1997) Alterations in the distribution of glutathione in the substantia nigra in Parkinson’s disease.J. Neural Trans. 104, 661–677.
Pierce, R.C., Rowlett, J.K., Rebec, G.V. and Bardo, M.T. (1995) Ascorbate potentiates amphetamine-induced conditioned place preference and forebrain dopamine release in rats.Brain Res. 688, 21–26.
Qian, Z.M., Tang, PL. and Wang, Q. (1997) Iron crosses the endosomal membrane by a carrier-mediated process.Pro. Biophys. Mol. Biol. 67, 1–15.
Rebec, G.V. and Pierce, R.C. (1994) A vitamin as neuromodulator: ascorbate release into the extracellular fluid of the brain regulates dopaminergic and glutamatergic transmission.Prog. Neurobiol. 43, 537–565.
Reddy, R.D. and Yao, J.K. (1996) Free radical pathology in schizphrenia: a review.Prost. Leuk. Ess. Fatty Acids 55, 33–43.
Reddy, R., Sahebarao, M.P, Mukherjee, S. and Murthy, J.N. (1991) Enzymes of the antioxidant defense system in chronic schizophrenic patients.Biol. Psychiatr. 30, 409–412.
Rouze, N.C. and Schwartz, E.A. (1998) Continuous and transient vesicle cycling at a ribbon synapse.J. Neurosci. 18, 8614–8624.
Sam, E.E. and Verbeke, N. (1995) Free radical scavenging properties of apomorphine enantiomers and dopamine: possible implication in their mechaism of action in Parkinsonism.J. Neural Trans. [Parkinson’s disease and Dementia section]10, 115–127.
Sassoe-Pognetto, M., Cantino, D., Panzanelli, P., Verdun di Cantogno, L., Giustetto, M., Margolis, E, De Biasi, L. and Fasolo, A. (1993) Presynaptic co-localization of carnosine and glutamate in olfactory neurons.NeuroReport 5, 7–10.
Sawada, H., Ibi, M., Kihara, T., Urushitani, M., Akaike, A., Kimura, J. and Shimohama, S. (1998) Dopamine D2-type agonists protect mesencephalic neurons from glutamate neurotoxicity: mechanisms of neuroprotective treatment against oxidative stress.Ann. Neurol. 44, 110–119.
Schapira, A.H.V., Mann, V.M., Cooper, J.M., Krige, D., Jenner, P.J. and Marsden, CD. (1992) Mitochondrial function in Parkinson’s disease.Ann. Neurol. 32, S116-S124.
Schipper, H.M., Liberman, A. and Stopa, E.G. (1998) Neural heme oxygenase-1 expression in ideopathic Parkinson’s disease.Exp. Neurol. 150, 60–68.
Schultz, W. (1997) Dopamine neurons and their role in reward mechanisms.Curr. Op. Neurobiol. 7, 191–197.
Schwartz, B.E., Sem-Jacobsen, C. and Petersen, M.C. (1956a) Effects of mescaline, LSD-25 and adrenochrome on depths electrograms in man.Arch. Neurol. Psychiatr. 75, 579–587.
Schwartz, B.E., Wakim, K.G. and Bickford, R. (1956b) Behavioral and electroencephalographic effects of hallucinogenic drugs: changes in cats on intraventricular injection.Arch. Neurol. Psychiatr. 75, 83–90.
Seitz, G., Gebhardt, S., Beck, J.F., Böhm, W., Lode, H.N., Niethammer, D. and Bruchelt, G. (1998) Ascorbic acid stimulates DOPA synthesis and tyrosine hydroxylase gene expression in the human neuroblastoma cell line SK-N-SH.Neurosci. Lett. 244, 33–36.
Sesack, S.R., Hawrylak, V.A., Matus, C., Guido, M.A. and Levey, A.I. (1998) Dopamine axon varicosities in the pre-limbic division of the rat prefrontal cortex exhibit sparse immunoreactivity for the dopamine transporter.J. Neurosci. 18, 2697–2708.
Shen, X.-M. and Dryhurst, G. (1996) Oxidation chemistry of (-) norepinephrine in the presence of L-cysteine.J. Med. Chem. 39, 2018–2029.
Skarpen, E., Johannessen, L.E., Bjerk, K., Fasteng, H., Guren, T.K., Lindeman, B., Thoresen, G.H., Christoffersen, T., Stang, E., Huitfeldt, H.S. and Madshus, I.H. (1998) Endocytosed epidermal growth factor (EGF) receptors contribute to the EGF-mediated growth arrest in A431 cells by inducing a sustained release of p21/CIPl.Exp. Cell. Res. 243, 161–172.
Smythies, J.R. (1996) On the function of neuromelanin.Proc. R. Soc. Lond. B. 263, 487–489.
Smythies, J.R. (1997) The biochemical basis of synaptic plasticity and neurocomputation: a new theory.Proc. R. Soc. Lond. B. 264, 575–579.
Smythies, J.R., Gottfries, C.-G. and Regland, B. (1997) Disturbances of one-carbon metabolism in neuropsychiatry disorders: a review.Biol. Psychiat. 41, 230–233.
Sorensen, S.D., Linseman, D.A., McEwan, EX., Heacock, A.M. and Fisher, S.K. (1998) A role for a wortmannin-sensitive phosphatidylinositol-4-kinase in the endocytosis of muscarinic cholinergic receptors.Mol. Pharmacol. 53, 827–836.
Szekeres, P.G., Koenig, J.A. and Edw’ardson, J.M. (1998) The relationship between agonist intrinsic activity and the rate of endocytosis of muscarinic receptors in a human neuroblastoma line.Mol. Pharmacol. 53, 759–763.
Taber, M.T. and Fibiger, H.C. (1997) Feeding-evoked dopamine release in the nucleus accumbens: regulation by glutamatergic mechanism.Neuroscience 76, 1105–1112.
Taubman, G. and Jantz, H. (1957) Untersuchung über die dem adrenochrom zugeschrieben psychotoxischen wirkungen.Nervenartz 28, 1957.
Toffa, S., Kunikowska, G.M., Zeng, B-Y, Jenner, P. and Marsden, CD. (1997) Glutathione depletion in rat brain does not cause nigrostriatal pathway degeneration.J. Neural. Trans. 104, 67–75.
Vandenbulcke, F., Nouel, D., Vincent, J.R and Beaudet, A. (1998) Differential intracellular trafficking of neurotensin and of its receptor in COS-7 transfected cells.Abst. Soc. Neurosci. 24, 1592.
Vickery, R.G., Christine, C. and von Zastrow, M. (1998) Subtype-specific differences in dopamine receptor endocytosis.Abst. Soc. Neurosci. 24, 23.
von Zastrow, M. and Kobilka, B.K. (1994) Antagonist-dependent and independent steps in the mechanism of adrenergic receptor internalization.J. Biol. Chem. 269, 18,448–18,452.
Vyoral, D. and Petr’ak, J. (1998) Iron transport in K562 cells: a kinetic study using native gel electrophoresis and59Fe autoradiography.Biochim. Biophys. Acta 1403, 179–188.
White, H.L. and Wu, J.C (1975) Properties of catechl O-methyl transferases from brain and liver of rat and human.Biochem. J. 145, 135–143.
Wolfe, L.S., Pappius, H.M. and Marion, J. (1976) The biosynthesis of prostaglandins by brain tissuein vitro.Adv. Prostaglandin Thromboxane Res. 1, 345–355.
Yao, J.K., Reddy, R.D., van Kammen, D.P., McElhiney, L.G. and Korbanic, C.W. (1998) Reduced level of the antioxidant proteins in schizophrenia.Biol. Psychiat. 43, 123S.
Yen, G.C and Hsieh, C.C. (1997) Antioxidant effects of dopamine and related compounds.Biosci. Biotech. Biochem. 61, 1646–1649.
Zapf-Colby, A. and Olefsky, J.M. (1998) Nerve growth factor processing and trafficking events following Trk-A-mediated endocytosis.Endocrinology 139, 3232–3240.
Zhang, J., Price, J.O., Graham, D.G. and Montine, T.J. (1998) Secondary excitotoxicity contributes to dopamine-induced apoptosis of dopaminergic neuronal cultures.Biochem. Biophys. Res. Com. 248, 812–816.
Zhao, Z.S., Khan, S. and O’Brien, P.J. (1998) Catecholic iron complexes as cytoprotective superoxide scavengers against hypoxia: reoxygenation injury in isolated hepatocytes.Biochem. Pharmacol. 56, 825–830.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Smythies, J. The neurotoxicity of glutamate, dopamine, iron and reactive oxygen species: Functional interrelationships in health and disease: A review — discussion. neurotox res 1, 27–39 (1999). https://doi.org/10.1007/BF03033337
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF03033337