Summary
Parkinson’s disease (PD) is a progressive neurological disorder caused by rather selective degeneration of the dopaminergic (DA) neurons in the substantia nigra. Though subject to intensive research, the etiology of this nigral neuronal loss is still enigmatic and treatment is basically symptomatic. The current major hypothesis suggests that nigral neuronal death in PD is due to excessive oxidative stress generated by auto-and enzymatic oxidation of the endogenous neurotransmitter dopamine (DA), the formation of neuromelanin and presence of high concentrations of iron.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Ahn BY, Moss B (1992) Glutaredoxin homologue encoded by vaccinia virus is a virion-ociated enzyme with thioltransferase and dehydroascorbate reductase activity. Proc Natl Acad Sci USA 89: 7060–7064
Anglade P, Vyas S, Javoy-Agid F, Herrero MT, Michel PP, Marquez J, Mouatt-Parignet A, Ruberg M, Hirsch EC, Agid Y (1997) Apoptosis and autophagy in nigral neurons of patients with Parkinson’s disease. Histol Histopathol 12: 25–31
Ben-Shachar D, Zuk R, Glinka Y (1995) Dopamine neurotoxicity: inhibition of mitochondrial respiration. J Neurochem 64: 718–723
Blin O, Desnuelle C, Rascol O, et al (1994) Mitochondrial respiratory failure in skeletal muscle from patient with Parkinson’s disease and multiple system atrophy. J Neurol Sci 125: 95–101
Bloom FE, Algeria S, Proppetti A, Revuelta A, Costa E (1969) Lesions of central orepinephrine terminals with 6-hydroxydopamine: biochemistry and fine structure. Science 166: 1284–1286
Chan P, Di Monte DA, Luo JJ, DeLanney LE, Irwin I, Langston JW (1994) Rapid ATP loss caused by methamphetamine in the mouse striatum: relationship between energy impairment and dopaminergic neurotoxicity. J Neurochem 62: 2484–2847
Chiueh CC, Miyake H, Peng MT (1993) Role of dopamine autoxidation, hydroxyl radical generation and calcium overload in underlying mechanisms involved in MPTPinduced parkinsonism. Adv Neurol 60: 251–258
Cohen G (1985) Oxidative stress in the nervous system. In: Sies H (ed) Oxidative stress. Academic Press, London, pp 383–401
Cohen G, Farooqui R, Kesler N (1997) Parkinson’s disease: A new link between monoamine oxidase and mitochondrial electron flow. Proc Natl Acad Sci USA 94: 4890–4894
Creagh EM, Cotter TG (1999) Selective protection by hsp 70 against cytotoxic drug-, but not Fas-induced T-cell apoptosis. Immunology 97: 36–44
Daily D, Barzilai A, Offen D, Kemsler A, Melamed E, Ziv I (1999) The involvement of p53 in dopamine induced apoptosis of cerebellar granule neurons and leukemic cells overexpressing p53. Mol Cell Neurobiol 19: 261–276
Fahn S, Cohen G (1992) The oxidant stress hypothesis in Parkinson’s disease. Evidence supporting it. Ann Neurol 32: 804–812
Feiner L, Koppel AM, Kobayashi H, Raper JA (1997) Secreted chick semaphorins bind recombinant neuropilin with similar affinities but bind different subsets of neurons in situ. Neuron 19: 539–545
Fillox F, Townsend JJ (1993) Pre-and postsynaptic neurotoxic effects of dopamine demonstrated by intrastriatal injection. Exp Neurol 119: 79–88
Fonstedt B (1990) Role of catechol autoxidation in the degeneration of dopamine neurons. Acta Neurol Scand 129: 12–14
Freyaldenhoven TE, Ali SF (1996) Heat shock proteins protect cultured fibroblasts from the cytotxic effects of MPP+. Brain Res 735: 42–49
Gabbay M, Tauber M, Porat S, et al (1996) Selective role of glutathione in protecting human neuronal cells from dopamine-induced apoptosis. Neuropharmacology 35: 571–578
Gagliardini V, Frankhauser C (1999) Semaphorin III can induce death in sensory neurons. Mol Cell Neurosci 14: 301–316
Galea-Lauri A, Richardson AJ, Latchman DS, Katz DR (1996) Increased heat shock protein 90 (hsp90) expression leads to increased apoptosis in the monoblastoid cell line U937 following induction with TNF-a and cycloheximide. J Immunol 157: 4109–4118
Gan ZR, Wells WW (1987) The primary structure of pig liver thioltrasferase. J Biol Chem 262: 6699–6703
Gan ZR, Polokoff MA, Jacobs JW, Sordana MK (1990) Complete amino acid sequence of yeast thiol transferase (glutaredoxin). Biochem Biophys Res Commun 168: 944–951
Gao Y, Thomas JO, Chow RL, Lee G-H, Cowan NJ (1992) A cytoplasmic chaperonin that catalyzes (3-actin foleling. Cell 69: 1043–1050
Gerlach M, Riederer P, Youdim MBH (1996) Molecular mechanisms for neurodegeneration: Synergism between reactive oxygen species, calcium and excitoxic amino acids. Adv Neurol 69: 177–197
Gerlach M, Xiao A, Heim C, Lan J, God R, Feineis D, Bringham G, Riederer P, Sontag KH (1998) 1-Trechloromethyl-1,2,3,4-tetrahydro-b-carboline (TaClo) increases extracellualr serotonin and stimulates hydroxyl radical production. Neurosci Lett: 257: 17–20
Goodman CS (1994) The likeness of being: Phylogenetically conserved molecular mechanisms of growth cone guidance. Cell 78: 353–356
Goshima Y, Nakamura F, Strittmatter P, Strittmatter SM (1995) Collapsin-induced growth cone collapse mediated by an intracellualr protein related to UNC-33. Nature 376: 509–514
Hastings TG, Zigmond MJ (1994) Identification of catechol-protein conjugates in neostriatal slices incubated with [3H1 dopamine: impact of ascorbic acid and glutathione. J Neurochem 63: 1126–1132
He Z, Tessier-Lavigne M (1997) Neuropilin is a receptor for the axonal chemorepellent semaphorin III. Cell 90: 739–751
Hirsch E, Hu LJ, Prignet A, Constatin B, Agid Y, Drabkin H, Roche J (1999) Distribution of semaphorin IV in adult human brain. Brain Res 823: 67–79
Hoog JO, Jornvall H, Holmgren A, Carlquist M, Persson M (1983) The primary structure of Escherichia coli glutaredoxin. Distant homology with thioredoxins in a superfamily of small proteins with a redox-active cystine disulfide/cysteine dithiol. Eur J Biochem 136: 223–232
Hopper S, Johnson RS, Biemann K (1989) Glutaredoxin from rabbit bone marrow. Purification, characterization and amino acid sequence determined by tandem mass spectrometry. J Biol Chem 264: 20438–20447
Janetzky B, Hauck S, Youdim MBH, et al (1994) Ulterated aconitase activity but decreased complex I activity in substantia nigra pars compacta of patients with Parkinson’s disease. Neurosci Lett 169: 126–128
Javitch JA, D’Amato RJ, Strittmatter SM, Snyder SH (1985) Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. Proc Natl Acad Sci USA 82: 2173–2177
Jenner P (1991) Oxidative stress as a cause of Parkinson’s disease. Acta Neurol Scand 136 Suppl: 6–15
Klintrot IM, Hoog JO, Jornvall H, Holmgren A, Luhtman M (1984) The primary structure of calf thymus glutaredoxin. Homology with the corresponding Escherichia coli protein but elongation at ends and with an additional half-cysteine/cysteine pair. Eur J Biochem 14: 417–413
Kolodkin AL (1996) Growth cones and the cues that repel them. Trends Neurosci 19: 507–513
Kolodkin AL, Levengood DV, Rowe EG, Tai Y, Giger RJ, Ginty DD (1997) Neuropilin is a semaphorin III receptor. Cell 90: 753–762
Koppel AM, Feiner L, Kobayashi H, Raper JA (1997) A 70 amino acid region within the semaphorin domain activates specific cellular response of semaphorin family members. Neuron 19: 531–537
Luo Y, Shepherd I, Li J, Renzi MJ, Chang S, Raper JA (1995) A family of molecules related to collapsin in the embryonic chick nervous system. Neuron 14: 1131–1140
Massenaro JM, Gong L, Kuage H, Baker I, Wyatt RJ (1996) Dopamine induces apoptotic cell death of cathecolaninergic cell line derived from the central nervous system. Mol Pharmacol 50: 1309–1315
McLaughlin BA, Nelson D, Erecinska M, Chesselet MF (1998) Toxicity of dopamine to striatal neurons in vitro and potentiation of cell death by a mitochondrial inhibitor. J Neurochem 70: 2406–2415
Michel PP, Hefti F (1990) Toxicity of 6-hydroxydopamine and dopamine for dopaminergic neurons in cell culture. J Neurosci Res 26: 428–435
Minakuchi K, Yabushita T, Masumura T, Ichihara K, Tanaka K (1994) Cloning and sequence analysis of a cDNA encoding rice glutaredoxin. FEBS Lett 337: 157–160 Mochizuki H, Mori H, Mizuno Y (1997) Apoptosis in neurodegenerative disorders. J Neural Transm Suppl 50: 157–160
Mytilineou C, Han SK, Cohen G (1993) Toxic and protective effects of L-DOPA on mesencephalic cell cultures. J Neurochem 61: 1470–1478
O’Dell SJ, Weihhmuller FB, Marshall JF (1993) Methamphetamine-induced dopamine terminals alteration by dopamine D1 and D2 antagonists. J Neurochem 60: 1792–1799
Offen D (1999) Personal communication
Offen D, Ziv I, Gorodin S, Malik Z, Barzilai A, Melamed E (1995) Dopamine-induced programmed cell death in mouse thymocytes. Biochim Biophys Acta 1268: 171–177
Offen D, Ziv I, Panet H, Wasserman L, Stein R, Melamed E, Barzilai A (1996) Dopamine-induced apoptosis is inhibited in PC12 cells expressing Bc1–2. Cell Mol Neurobiol 17: 1–2
Padilla CA, Martinez-Galisteo E, Barcenea JA, Spyrou G, Holmgren A (1995) Purification from placenta, amino acid sequence, structure comparison and cDNA cloninig of human glutaredoxin. Eur J Biochem 227: 27–34
Parker WD, Boyson SJ, Parks JK (1989) Abnormalities in electron transport chain in idiopathic Parkinson’s disease. Ann Neurol 26: 719–723
Przedborski S, Jackson-Lewis V, Muthane U, Jiang H, Ferreira M, Naini AB, Fahn S (1993) Chronic levodopa administration alters cerebral mitochondrial respiratory chain activity. Ann Neurol 34: 715–723
Punyiczki M, Fesus L (1998) Heat shock and apoptosis; The two defense systems of the organism may have overlapping molecular elements. Ann N Y Acad Sci 851: 67–74
Putcha GV, Deshmukh M, Johnson Jr EM (1999) BAX translocation is a critical event in neuronal apoptosis: regulation by neuroprotectants, BCL-2, and caspases. J Neurosci 19: 7476–7485
Ramsay RR, Krueger MJ, Youngster SK, Gluck MR, Casida JE, Singer TP (1991) Interaction of 1-methyl-4-phenylpyridium ion (MPP+) and its analogs with rotenone/ piericidin binding site of NADH dehydrogenase. J Neurochem 56: 1184–1190
Riederer PE, Sofic W, Rausch D, Schmidt B, Reynolds GP, Jellinger K, Youdim MBH (1989) Transition metals ferritin, gltathione, and ascorbic acid in parkinsonian brains. J Neurochem 52: 515–520
Rosenberg PA (1988) Catecholamine toxicity in cerebral cortex of dissociated cell cultur. J Neurosci 8: 2887–2894
Ruberg M, France-Leonard V, Brugg B, Lambeng N, Michel PP, Anglade P, Hunot ST, Damier P, Faucheux B, Hirsch E, Agid Y (1997) Neuronal death caused by apoptosis in Parkinson disease. Rev Neurol 153(8–9): 8–9
Samali A, Cai J, Zhivotovsky B, Jones DP, Orrenius S (1999) Presence of pre-apoptotic complex of pro-caspase-3, Hsp60 and Hsp10 in the mitochondrial fraction of Jurkat cells. EMBO J 18: 2040–2048
Schapira AHV, Cooper JM, Dexter D (1990) Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem 54: 823–827
Shirvan A, Ziv I, Machlin T, Zilkha-Falb R, Melamed E, Barzilai A (1997) Two waves of cyclin B and proliferating nuclear antigen expression during dopamine-triggered neuronal apoptosis. J Neurochem 69: 539–549
Shirvan A, Ziv I, Fleminger G, Shina R, He Z, Brudo I, Melamed E, Barzilai A (1999) Semaphorins as mediators of apoptosis. J Neurochem 73: 961–971
Simantov R, Blinder E, Ratovitski T, Tauber M, Gabbay M, Porat S (1996) Dopamine induced apoptosis in human neural cells: inhibition by nucleic acid antisense to the dopamine transporter. Neurosci 74: 39–50
Sirinathsinghji DJ, Heavens RP, McBribde CS (1988) Dopamine-releasing action of 1methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) and 1-methyl-4-phenylpyridine (MPP+) in the neostriatum of the rat. Brain Res 443: 101–116
Sternlicht H, Farr GW, Sternlicht ML, Driscoll JK, Willison K, Yaffe MB (1993) The tomplex polypeptide 1 complex is a chaperonin for tubulin and actin in vivo. Proc Natl Acad Sci USA 90: 9422–9426
Tanaka M, Sotomatsu A, Kanai H, Hirai S (1991) DOPA and dopamine cause cultured neuronal death in the presence of iron. J Neurochem 101: 198–203
Tatton NA, Maclean-Fraser A, Tatton WG, Perl DP, Olanow CW (1998) A fluorescent double-labeling method to detect and confirm apoptotic nuclei in parkinson’s disease. Ann Neurol 44(3) Suppl 1: S142–148
Tessier-Lavigne M, Goodman CS (1996) The molecular biology of axon guidance. Science 274: 1123–1131
Wang LH, Strittmatter SM (1996) A family of rat CRMP genes is differentially expressed in the neurvous system. J Neurosci 16: 6197–6207
Xanthoudakis S, Roy S, Rasper D, Hennessey T, Aubin Y, Cassady R, Tawa P, Ruel R, Rosen A, Nicholson DW (1999) Hsp60 accelerates the maturation of procaspase-3 by upstream activator proteases during apoptosis. EMBO J 18: 2049–2056
Yaffe MB, Farr GW, Miklos D, Horwich AL, Sternlicht ML, Sternlicht H (1992) TCP-1 complex is a molecular chaperone in tubulin biogenesis. Nature 358: 245–248
Youdim MBH, Ben-Shachar D, Riederer P (1993a) The possible role of iron in the ethiology of Parkinson’s disease. Mov Disord 8: 1–14
Youdim MBH, Ben-Shachar D, Riederer P (1993b) Iron melanin interaction and Parkinson’s disease. Trends Pharmacol Sci 8: 45–49
Zilkha-Falb R, Ziv I, Offen D, Melamed E, Barzilai A (1997) Monoamines-induced apoptotic neuronal cell death. Cell Mol Neurobiol 17: 101–118
Zilkha-Falb R, Barzilai A, Djaldeti R, Ziv I, Machlin T, Melamed E, Shirvan A (2000) Involvement of T-complex Protein-1 (TCP-1) in dopamine triggered neuronal apoptosis in chick embryo sympathetic neurons. Submitted
Ziv I, Melamed E, Nardi N, et al (1994) Dopamine induced apoptosis-like cell death in cultured chick sympathetic neurons-a possible novel pathogenetic mechanism in Parkinson’s disease. Neurosci Lett 170: 136–140
Ziv I, Offen D, Haviv R, Stein R, Achiron A, Panet H, Barzilai A, Melamed E (1997) The protooncogene bc1–2 inhibits cellular toxicity of dopamine: Possible implication for Parkinson’s disease. Apoptosis 2: 1–2
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2000 Springer-Verlag Wien
About this paper
Cite this paper
Barzilai, A. et al. (2000). The molecular mechanism of dopamine-induced apoptosis: identification and characterization of genes that mediate dopamine toxicity. In: Riederer, P., et al. Advances in Research on Neurodegeneration. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6301-6_4
Download citation
DOI: https://doi.org/10.1007/978-3-7091-6301-6_4
Publisher Name: Springer, Vienna
Print ISBN: 978-3-211-83537-1
Online ISBN: 978-3-7091-6301-6
eBook Packages: Springer Book Archive