Conclusions

The Parkinson's-Reversing Breakthrough

Diets for Parkinsons

Get Instant Access

The discovery that MPTP, which is structurally similar to a number of commonly used herbicides and pesticides, can induce specific loss of substantia nigra neurons in many vertebrate species, from humans to mice, has lead to the development of a useful model of Parkinson disease. In mice, MPTP demonstrates differential toxicity that is dependent on the strain of animal examined (Sonsalla and Heikkila 1988; Muthane et al. 1994; Hamre et al. 1999). This finding supports the hypothesis that the loss of substantia nigra neurons in Parkinson disease may result from a genetic sensitivity to a number of environmental agents (Veldman et al. 1998; Stoessl 1999). In a recent study, the chromosomal loci containing the genetic sequences responsible for this sensitivity was identified on the telomeric end of mChr.1 (Cook et al. 2003). Further studies into the genetic and biochemical pathways involved in MPTP toxicity will lead to a better understanding of idiopathic Parkinson disease and provide clues to novel targets for therapeutic interventions.

References

Ara, J., S. Przedborski, A.B. Naini, V. Jackson-Lewis, R.R. Trifiletti, J. Horwitz, and H. Ischiropoulos. 1998. Inactivation of tyrosine hydroxylase by nitration following exposure to peroxynitrite and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Proc Natl Acad Sci U S A 95:7659-7663.

Aulak, K.S., M. Miyagi, L. Yan, K.A. West, D. Massillon, J.W. Crabb, and D.J. Stuehr. 2001. Proteomic method identifies proteins nitrated in vivo during inflammatory challenge. Proc Natl Acad Sci U S A 98:1205612061.

Beal, M.F. 2003. Mitochondria, oxidative damage, and inflammation in

Parkinson's disease. Ann N Y Acad Sci 991:120-131. Betarbet, R., T.B. Sherer, G. MacKenzie, M. Garcia-Osuna, A.V. Panov, and J.T. Greenamyre. 2000. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci 3:13011306.

Bezard, E., C.E. Gross, M.C. Fournier, S. Dovero, B. Bloch, and M. Jaber. 1999. Absence of MPTP-induced neuronal death in mice lacking the dopamine transporter. Exp Neurol 155:268-273. Brecknell, J.E., S.B. Dunnett, and J.W. Fawcett. 1995. A quantitative study of cell death in the substantia nigra following a mechanical lesion of the medial forebrain bundle. Neurosci 64:219-227. Brooks, A.I., C.A. Chadwick, H.A. Gelbard, D.A. Cory-Slechta, and H.J. Federoff. 1999. Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss. Brain Res 823:1-10. Brooks, W.J., M.F. Jarvis, and G.C. Wagner. 1989. Astrocytes as a primary locus for the conversion MPTP into MPP+. J Neural Transm 76:1-12. Burns, R.S., P. LeWitt, M.H. Ebert, H. Pakkenberg, and I.J. Kopin. 1985. The clinical syndrome of striatal dopamine deficiency; parkinsonism induced by MPTP. N Engl J Med 312:1418-1421. Cassina, A.M., R. Hodara, J.M. Souza, L. Thomson, L. Castro, H. Ischiropoulos, B.A. Freeman, and R. Radi. 2000. Cytochrome c nitration by peroxynitrite. J Biol Chem 275:21409-21415. Cerruti, C., D.M. Walther, M.J. Kuhar, and G.R. Uhl. 1993. Dopamine transporter mRNA expression is intense in rat midbrain neurons and modest outside midbrain. Mol Brain Res 18:181-186. Cheng, F.C., D.R. Ni, M.C. Wu, J.S. Kuo, and L.G. Chia. 1998. Glial cell line-derived neurotrophic factor protects against 1-methyl-4-phenyl-

1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in C57BL/6 mice. Neurosci Lett 252:87-90.

Chun, H.S., G.E. Gibson, L.A. DeGiorgio, H. Zhang, V.J. Kidd, and J.H. Son. 2001. Dopaminergic cell death induced by MPP(+), oxidant and specific neurotoxicants shares the common molecular mechanism. JNeurochem 76:1010-1021.

Cleeter, M.W., J.M. Cooper, and A.H. Schapira. 1992. Irreversible inhibition of mitochondrial complex I by 1-methyl-4-phenylpyridinium: evidence for free radical involvement. J Neurochem 58:786-789.

Conway, K.A., J.D. Harper, and P.T. Lansbury. 1998. Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease. Nat Med 4:1318-1320.

Cook, R., L. Lu, J. Gu, R.W. Williams, and R.J. Smeyne. 2003. Identification of a single QTL, Mptp1, for susceptibility to MPTP-induced sub-stantia nigra pars compacta neuron loss in mice. Mol Brain Res 110:279-288.

D'Amato, R.J., Z.P. Lipman, and S.H. Snyder. 1986. Selectivity of the parkinsonian neurotoxin MPTP: toxic metabolite MPP+ binds to neu-romelanin. Science 231:987-989.

Damier, P., E.C. Hirsch, Y. Agid, and A.M. Graybiel. 1999. The substantia nigra of the human brain. II. Patterns of loss of dopamine-containing neurons in Parkinson's disease. Brain 122:1437-1448.

Date, I., M. Aoi, S. Tomita, F. Collins, and T. Ohmoto. 1998. GDNF administration induces recovery of the nigrostriatal dopaminergic system both in young and aged parkinsonian mice. Neuroreport 9:2365-2369.

Daubner, S.C., D.L. Lohse, and P.F. Fitzpatrick. 1993. Expression and characterization of catalytic and regulatory domains of rat tyrosine hydrox-ylase. Protein Sci 2:1452-1460.

de Rijk, M.C., M.M. Breteler, G.A. Graveland, A. Ott, D.E. Grobbee, F.G. van der Meche, and A. Hofman. 1995. Prevalence of Parkinson's disease in the elderly: the Rotterdam Study. Neurology 45:2143-2146.

Del Zompo, M., M.P. Piccardi, S. Ruiu, M. Quartu, G.L. Gessa, and A. Vaccari. 1993. Selective MPP+ uptake into synaptic dopamine vesicles: possible involvement in MPTP neurotoxicity. Br J Pharm 109:411-414.

Deumens, R., A. Blokland, and J. Prickaerts. 2002. Modeling Parkinson's disease in rats: an evaluation of 6-OHDA lesions of the nigrostriatal pathway. Exp Neurol 175:303-317.

Di Monte, D., M.S. Sandy, G. Ekstrom, and M.T. Smith. 1986. Comparative studies on the mechanisms of paraquat and 1-methyl-4-phenylpyridine (MPP+) cytotoxicity. Biochem Biophys Res Commun 137:303-309.

Di Monte, D.A., J.E. Royland, I. Irwin, and J.W. Langston. 1996. Astro-cytes as the site for bioactivation of neurotoxins. Neurotoxicology 17:697-703.

Di Monte, D.A., E.Y. Wu, I. Irwin, L.E. Delanney, and J.W. Langston. 1992. Production and disposition of 1-methyl-4-phenylpyridinium in primary cultures of mouse astrocytes. Glia 5:48-55.

Dringen, R., B. Pfeiffer, and B. Hamprecht. 1999. Synthesis of the antiox-idant glutathione in neurons: supply by astrocytes of CysGly as precursor for neuronal glutathione. J Neurosci 19:562-569.

Drukarch, B., E. Schepens, J.C. Stoof, C.H. Langeveld, and F.L. Van Muiswinkel. 1998. Astrocyte-enhanced neuronal survival is mediated by scavenging of extracellular reactive oxygen species. Free Rad Biol Med 25:217-220.

Duvoisin, R.C. 1999. Genetic and environmental factors in Parkinson's disease. Adv Neurology 80:161-163.

Elbirt, K.K., and H.L. Bonkovsky. 1999. Heme oxygenase: recent advances in understanding its regulation and role. Proc Assoc Am Physicians 111: 438-447.

Fahn, S., and S. Przedborski. 2000. Parkinsonism. In Merritt's Neurology, 10th Edition Ed. L.P. Rowland. pp 679-693. Philadelphia: Lippincott Williams and Wilkins.

Faull, R.L., and W.R. Mehler. 1978. The cells of origin of nigrotectal, nigrothalamic and nigrostriatal projections in the rat. Neuroscience 3:989-1002.

Fernandez-Gonzales, A., I. Perez-Otano, and J.I. Morgan. 2000. MPTP selectively induces heme oxygenase-1 expression in striatal astrocytes. Eur J Neurosci 12:1573-1583.

Fornai, F., G. Battaglia, M. Gesi, F.S. Giorgi, F. Orzi, F. Nicoletti, and S. Ruggieri. 2000. Time-course and dose-response study on the effects of chronic L-dopa administration on striatal dopamine levels and dopamine transporter following MPTP toxicity. Brain Res 887: 110-117.

Forno, L.S., L.E. DeLanney, I. Irwin, D. Di Monte, and J.W. Langston. 1992. Astrocytes and Parkinson's disease. Prog Brain Res 94:429-436.

Frim, D.M., T.A. Uhler, W.R. Galpern, M.F. Beal, X.O. Breakefield, and O. Isacson. 1994. Implanted fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevent 1-methyl-4-phenylpyridinium toxicity to dopaminergic neurons in the rat. Proc Natl Acad Sci U S A 91:5104-5108.

Gainetdinov, R.R., F. Fumagalli, S.R. Jones, and M.G. Caron. 1997. Dopamine transporter is required for in vivo MPTP neurotoxicity: evidence from mice lacking the transporter. J Neurochem 69: 1322-1325.

Gainetdinov, R.R., F. Fumagalli, Y.M. Wang, S.R. Jones, A.I. Levey, G.W. Miller, and M.G. Caron. 1998. Increased MPTP neurotoxicity in vesicular monoamine transporter 2 heterozygote knockout mice. J Neurochem 70:1973-1978.

Gasser, T. 2001. Genetics of Parkinson's disease. J Neurol 248:833-840.

German, D.C., K. Manaye, W.K. Smith, D.J. Woodward, and C.B. Saper. 1989. Midbrain dopaminergic cell loss in Parkinson's disease: computer visualization. Ann Neurol 26:507-514.

Giasson, B.I., R. Jakes, M. Goedert, J.E. Duda, S. Leight, J.Q. Trojanowski, and V.M. Lee. 2000a. A panel of epitope-specific antibodies detects protein domains distributed throughout human alpha-synuclein in Lewy bodies of Parkinson's disease. J Neurosci Res 59:528-533.

Giasson, B.I., J.E. Duda, I.V. Murray, Q. Chen, J.M. Souza, H.I. Hurtig, H. Ischiropoulos, J.Q. Trojanowski, and V.M. Lee. 2000b. Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science 290:985-989.

Gong, L., R.J. Wyatt, I. Baker, and J.M. Masserano. 1999. Brain-derived and glial cell line-derived neurotrophic factors protect a catecholamin-ergic cell line from dopamine-induced cell death. Neurosci Lett 263: 153-156.

Graham, D.G. 1978. Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol 14:633-643.

Grofova, I. 1979. Extrinsic connections of the neostriatum. In The Neo-striatum. Ed. I. Divac and R.G.E. Oberg . pp 37-51. Oxford: Pergamon Press.

Hadjiconstantinou, M., J.G. Fitkin, A. Dalia, and N.H. Neff. 1991. Epidermal growth factor enhances striatal dopaminergic parameters in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mouse. J Neurochem 57:479-482.

Hamre, K., R. Tharp, K. Poon, X. Xiong, and R.J. Smeyne. 1999. Differential strain susceptibility following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration acts in an autosomal dominant fashion: quantitative analysis in seven strains of Mus musculus. Brain Res 828:91-103.

Hansen, T.W. 1994. Bilirubin in the brain. Distribution and effects on neu-rophysiological and neurochemical processes. Clin Pediatr (Phila) 33:452-459.

Hastings, T.G. 1995. Enzymatic oxidation of dopamine: the role of prostaglandin H synthase. J Neurochem 64:919-924.

Hatakeyama, S., Y. Hayasaki, M. Masuda, A. Kazusaka, and S. Fujita. 1996. Mechanism for mouse strain differences in the protective effect of Sudan III against the in vivo genotoxicity of 7,12-dimethyl-benz[a]anthracene. Tox Lett 89:231-239.

Hazell, A.S., Y. Itzhak, H. Liu, and M.D. Norenberg. 1997. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) decreases glutamate uptake in cultured astrocytes. J Neurochem 68:2216-2219.

Heaton, M.B., M. Paiva, I. Madorsky, J. Mayer, and D.B. Moore. 2003. Effects of ethanol on neurotrophic factors, apoptosis-related proteins, endogenous antioxidants, and reactive oxygen species in neonatal striatum: relationship to periods of vulnerability. Dev Brain Res 140:237-252.

Higuchi, S., T. Muramatsu, H. Arai, M. Hayashida, H. Sasaki, and J.Q. Trojanowski. 1995. Polymorphisms of dopamine receptor and transporter genes and Parkinson's disease. J Neural Transn 10:107-113.

Hirrlinger, J., J.B. Schulz, and R. Dringen. 2002. Effects of dopamine on the glutathione metabolism of cultured astroglial cells: implications for Parkinson's disease. J Neurochem 82:458-467.

Hirsch, E.C., and S. Hunot. 2000. Nitric oxide, glial cells and neuronal degeneration in parkinsonism. TIPS 21:163-165.

Hirsch, E.C., S. Hunot, P. Damier, and B. Faucheux. 1998. Glial cells and inflammation in Parkinson's disease: a role in neurodegeneration?. Ann Neurol 44:S115-120.

Hirsch, E.C., G. Hoglinger, E. Rousselet, T. Breidert, K. Parain, J. Feger, M. Ruberg, A. Prigent, C. Cohen-Salmon, and J.M. Launay. 2003. Animal models of Parkinson's disease in rodents induced by toxins: an update. J Neural Transm Suppl:89-100.

Hu, C.J., S.M. Sung, H. Liu, and J.G. Chang. 1999. No mutation of G209A in the alpha-synuclein gene in sporadic Parkinson's disease among Taiwan Chinese. Eur Neurol 41:85-87.

Hunot, S., F. Boissiere, B. Faucheux, B. Brugg, A. Mouatt-Prigent, Y. Agid, and E.C. Hirsch. 1996. Nitric oxide synthase and neuronal vulnerability in Parkinson's disease. Neuroscience 72:355-363.

Hunot, S., N. Dugas, B. Faucheux, A. Hartmann, M. Tardieu, P. Debre, Y Agid, B. Dugas, and E.C. Hirsch. 1999. FcepsilonRII/CD23 is expressed in Parkinson's disease and induces, in vitro, production of nitric oxide and tumor necrosis factor-alpha in glial cells. J Neurosci 19:3440-3447.

Inazu, M., H. Takeda, and T. Matsumiya. 2003. Expression and functional characterization of the extraneuronal monoamine transporter in normal human astrocytes. J Neurochem 84:43-52.

Ischiropoulos, H., and A.B. al-Mehdi. 1995. Peroxynitrite-mediated oxida-tive protein modifications. FEBSLett 364:279-282.

Jackson-Lewis, V., M. Jakowec, R.E. Burke, and S. Przedborski. 1995. Time course and morphology of dopaminergic neuronal death caused by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neurodegeneration 4:257-269.

Jellinger, K.A. 1999. The role of iron in neurodegeneration: prospects for pharmacotherapy of Parkinson's disease. Drugs Aging 14:115-140.

Jenner, P. 2003. The contribution of the MPTP-treated primate model to the development of new treatment strategies for Parkinson's disease. Parkinsonism Relat Disord 9:131-137.

Kalaria, R.N., M.J. Mitchell, and S.I. Harik. 1987. Correlation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity with blood-brain barrier monoamine oxidase activity. Proc Natl Acad Sci U S A 84: 3521-3525.

Khan, F.H., T. Sen, and S. Chakrabarti. 2003. Dopamine oxidation products inhibit Na+, K+-ATPase activity in crude synaptosomal-mitochondrial fraction from rat brain. Free Radic Res 37:597-601.

Kirschner, P.B., B.G. Jenkins, J.B. Schulz, S.P. Finkelstein, R.T. Matthews, B.R. Rosen, and M.F. Beal. 1996. NGF, BDNF and NT-5, but not NT-3 protect against MPP+ toxicity and oxidative stress in neonatal animals. Brain Res 713:178-185.

Kitayama, S., J.B. Wang, and G.R. Uhl. 1993. Dopamine transporter mutants selectively enhance MPP+ transport. Synapse 15:58-62.

Klivenyi, P., D. St Clair, M. Wermer, H.C. Yen, T. Oberley, L. Yang, and M. Flint Beal. 1998. Manganese superoxide dismutase overexpression attenuates MPTP toxicity. Neurobiol Dis 5:253-258.

Kopin, I.J. 1992. Features of the dopaminergic neurotoxin MPTP. Ann NY Acad Sci 648:96-104.

Kopin, I.J., and S.P. Markey. 1988. MPTP toxicity: implications for research in Parkinson's disease. Annu Rev Neurosci 11:81-96.

Lancaster, J.R., Jr. 1996. Diffusion of free nitric oxide. Methods Enzymol 268:31-50.

Lander, E.S., and N.J. Schork. 1994. Genetic dissection of complex traits. Science 265:2037-2048.

Langston, J.W. 1985. The case of the tainted heroin. The Sciences 25:34-40.

Langston, J.W., and J. Palfreman. 1996. The Case of the Frozen Addicts. New York: Vintage Books.

Lau, Y.S., Y.K. Fung, K.L. Trobough, J.R. Cashman, and J.A. Wilson. 1991. Depletion of striatal dopamine by the N-oxide of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Neurotoxicology 12:189-199.

LaVoie, M.J., and T.G. Hastings. 1999. Peroxynitrite- and nitrite-induced oxidation of dopamine: implications for nitric oxide in dopaminergic cell loss. JNeurochem 73:2546-2554.

Le Couteur, D.G., P.W. Leighton, S.J. McCann, and S. Pond. 1997. Association of a polymorphism in the dopamine-transporter gene with Parkinson's disease. Movement Dis 12:760-763.

Levine, M.S., C.D. Hull, R.S. Fisher, N.A. Buchwald, and A. Heller. 1983. Effects of neonatal destruction of the medial forebrain bundle in the cat: long-term neurochemical, locomotor, and regulatory deficits. Exp Neurol 81:340-358.

Liberatore, G.T., V. Jackson-Lewis, S. Vukosavic, A.S. Mandir, M. Vila, W.G. McAuliffe, V.L. Dawson, T.M. Dawson, and S. Przedborski. 1999. Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease. Nat Med 5:1403-1409.

Liu, Y., D. Peter, A. Roghani, S. Schuldiner, G.G. Prive, D. Eisenberg, N. Brecha, and R.H. Edwards 1992. AcDNAthat suppresses MPP+ toxicity encodes a vesicular amine transporter. Cell 70:539-551.

MacMillan-Crow, L.A., J.P. Crow, J.D. Kerby, J.S. Beckman, and J.A. Thompson. 1996. Nitration and inactivation of manganese superoxide dismutase in chronic rejection of human renal allografts. Proc Natl Acad Sci U S A 93:11853-11858.

Maines, M.D. 1997. The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol 37:517-554.

Maines, M.D. 2000. The heme oxygenase system and its functions in the brain. Cell Mol Biol (Noisy-le-grand) 46:573-585.

Marini, A.M., R.H. Lipsky, J.P. Schwartz, and I.J. Kopin 1992. Accumulation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in cultured cere-bellar astrocytes. J Neurochem 58:1250-1258.

McGeer, P.L., and E.G. McGeer. 1998. Glial cell reactions in neurodegen-erative diseases: pathophysiology and therapeutic interventions. Alz Dis Assoc Dis 12 Suppl 2:S1-6.

McNaught, K.S., U. Thull, P.A. Carrupt, C. Altomare, S. Cellamare, A. Carotti, B. Testa, P. Jenner, and C.D. Marsden. 1996. Effects of iso-quinoline derivatives structurally related to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on mitochondrial respiration. Biochem Pharmacol 51:1503-1511.

McNaught, K.S.P., and P. Jenner. 1999. Altered glial function causes neuronal death and increases neuronal susceptibility to 1-methyl-4-phenylpyridium and 6-hydroxydopamine induced toxicity in astrocytic/ ventral mesencephalic co-cultures. J Neurochem 73:2469-2476.

Melamed, E., D. Offen, A. Shirvan, and I. Ziv. 2000. Levodopa—an exotoxin or a therapeutic drug? J Neurol 247 Suppl 2:II135-139.

Miller, G.W., R.R. Gainetdinov, A.I. Levey, and M.G. Caron. 1999a. Dopamine transporters and neuronal injury. TIPS 20:424-429.

Miller, G.W., J.D. Erickson, J.T. Perez, S.N. Penland, D.C. Mash, D.B. Rye, and A.I. Levey. 1999b. Immunochemical analysis of vesicular monoamine transporter (VMAT2) protein in Parkinson's disease. Exp Neurol 156:138-148.

Mitra, N., K.P. Mohanakumar, and D.K. Ganguly. 1994. Resistance of golden hamster to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: relationship with low levels of regional monoamine oxidase B. J Neu-rochem 62:1906-1912.

Mizuno, Y., N. Sone, K. Suzuki, and T. Saitoh. 1988a. Studies on the toxicity of 1-methyl-4-phenylpyridinium ion (MPP+) against mitochondria of mouse brain. J Neurol Sci 86:97-110.

Mizuno, Y., N. Sone, K. Suzuki, and T. Saitoh. 1988b. Studies on the toxicity of 1-methyl-4-phenylpyridinium ion (MPP+) against mitochondria of mouse brain. J Neurol Sci 86:97-110.

Muller, T., T. Buttner, A.F. Gholipour, and W. Kuhn. 2003. Coenzyme Q10 supplementation provides mild symptomatic benefit in patients with Parkinson's disease. Neurosci Lett 341:201-204.

Muthane, U., K.A. Ramsay, H. Jiang, V. Jackson-Lewis, D. Donaldson, S. Fernando, M. Ferreira, and S. Przedborski. 1994. Differences in nigral neuron number and sensitivity to 1-methyl-4-phenyl-1,2,3,6-tetrahy-dropyridine in C57/bl and CD-1 mice. Exp Neurol 126:195-204.

Nagatsu, T., M. Mogi, H. Ichinose, and A. Togari. 2000. Changes in cytokines and neurotrophins in Parkinson's disease. J Neural Transm Suppl:277-290.

Nakajima, K., H. Hida, Y. Shimano, I. Fujimoto, T. Hashitani, M. Kumazaki, T. Sakurai, and H. Nishino. 2001. GDNF is a major component of trophic activity in DA-depleted striatum for survival and neurite extension of DAergic neurons. Brain Res 916:76-84.

Nicklas, W.J., I. Vyas, and R.E. Heikkila. 1985. Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenyl-pyridine, a metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,5,6-tetrahydropy-ridine. Life Sci 36:2503-2508.

Nicklas, W.J., S.K. Youngster, M.V. Kindt, and R.E. Heikkila. 1987. MPTP, MPP+ and mitochondrial function. Life Sci 40:721-729.

Nurmi, E., H.M. Ruottinen, J. Bergman, M. Haaparanta, O. Solin, P. Sonninen, and J.O. Rinne. 2001. Rate of progression in Parkinson's disease: a 6-[18F]fluoro-L-dopa PET study. Mov Disord 16:608-615.

Nussbaum, R.L., and M.H. Polymeropoulos. 1997. Genetics of Parkinson's disease. Hum Mol Gen 6:1687-1692.

O'Banion, M.K. 1999. COX-2 and Alzheimer's disease: potential roles in inflammation and neurodegeneration. Expert Opin Investig Drugs 8:1521-1536.

Ofori, S., and M. Schorderet. 1987. Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on dopamine synthesis and release in the rabbit retina in vitro. Neuropharm 26:1607-1610.

Olney, J.W., C.F. Zorumski, G.R. Stewart, M.T. Price, G.J. Wang, and J. Labruyere. 1990. Excitotoxicity of L-dopa and 6-OH-dopa: implications for Parkinson's and Huntington's diseases. Exp Neurol 108:269-272.

Otto, D., and K. Unsicker. 1994. FGF-2 in the MPTP model of Parkinson's disease: effects on astroglial cells. Glia 11:47-56.

Parkinson, J. 1817. An essay on shaking palsy. London: Sherwood, Neeley and Jones.

Payami, H., and S. Zareparsi. 1998. Genetic epidemiology of Parkinson's disease. J Ger Psych Neurol 11:98-106.

Petersen, A.A., K.E. Larsen, G.G. Behr, N. Romero, S. Przedborski, P. Brundin, and D. Sulzer. 2001. Brain-derived neurotrophic factor inhibits apoptosis and dopamine-induced free radical production in stri-atal neurons but does not prevent cell death. Brain Res Bull 56:331-335.

Polymeropoulos, M.H., C. Lavedan, E. Leroy, S.E. Ide, A. Dehejia, A. Dutra, B. Pike, H. Root, J. Rubenstein, R. Boyer, E.S. Stenroos, S. Chandrasekharappa, A. Athanassiadou, T. Papapetropoulos, W.G. Johnson, A.M. Lazzarini, R.C. Duvoisin, G. Di Iorio, L.I. Golbe, and R.L. Nussbaum. 1997. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276:2045-2047.

Poss, K.D., and S. Tonegawa 1997. Heme oxygenase 1 is required for mammalian iron reutilization. Proc Natl Acad Sci U S A 94:10919-10924.

Przedborski, S., and V. Jackson-Lewis. 1998. Mechanisms of MPTP toxi-city. Mov Disord 13 Suppl 1:35-38.

Przedborski, S., and M. Vila. 2003. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model: a tool to explore the pathogenesis of Parkinson's disease. Ann N Y Acad Sci 991:189-198.

Przedborski, S., V. Jackson-Lewis, R. Yokoyama, T. Shibata, V.L. Dawson, and T.M. Dawson. 1996. Role of neuronal nitric oxide in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neu-rotoxicity. Proc Natl Acad Sci U S A 93:4565-4571.

Przedborski, S., V. Jackson-Lewis, R. Djaldetti, G. Liberatore, M. Vila, S. Vukosavic, and G. Almer. 2000. The parkinsonian toxin MPTP: action and mechanism. Rest Neurol Neurosci 16:135-142.

Przedborski, S., V. Kostic, V. Jackson-Lewis, A.B. Naini, S. Simonetti, S. Fahn, E. Carlson, C.J. Epstein, and J.L. Cadet. 1992. Transgenic mice with increased Cu/Zn-superoxide dismutase activity are resistant to N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity. J Neurosci 12:1658-1667.

Przedborski, S., Q. Chen, M. Vila, B.I. Giasson, R. Djaldatti, S. Vukosavic, J.M. Souza, V. Jackson-Lewis, V.M. Lee, and H. Ischiropoulos. 2001. Oxidative post-translational modifications of alpha-synuclein in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. J Neurochem 76:637-640.

Quijano, C., D. Hernandez-Saavedra, L. Castro, J.M. McCord, B.A. Freeman, and R. Radi. 2001. Reaction of peroxynitrite with Mn-superoxide dismutase. Role of the metal center in decomposition kinetics and nitration. J Biol Chem 276:11631-11638.

Radi, R., A. Cassina, R. Hodara, C. Quijano, and L. Castro. 2002. Per-oxynitrite reactions and formation in mitochondria. Free Radic Biol Med 33:1451-1464.

Ramsay, R.R., and T.P. Singer. 1986. Energy-dependent uptake of N-methyl-4-phenylpyridinium, the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, by mitochondria. J Biol Chem 261:7585-7587.

Ramsay, R.R., J. Dadgar, A. Trevor, and T.P. Singer. 1986. Energy-driven uptake of N-methyl-4-phenylpyridine by brain mitochondria mediates the neurotoxicity of MPTP. Life Sci 39:581-588.

Ransom, B.R., D.M. Kunis, I. Irwin, and J.W. Langston. 1987. Astrocytes convert the parkinsonism inducing neurotoxin, MPTP, to its active metabolite, MPP+. Neurosci Lett 75:323-328.

Riachi, N.J., and S.I. Harik. 1988. Strain differences in systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity in mice correlate best with monoamine oxidase activity at the blood-brain barrier. Life Sci 42:2359-2363.

Riachi, N.J., W.D. Dietrich, and S.I. Harik. 1990. Effects of internal carotid administration of MPTP on rat brain and blood-brain barrier. Brain Res 533:6-14.

Riachi, N.J., S.I. Harik, R.N. Kalaria, and L.M. Sayre. 1988. On the mechanisms underlying 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity. II. Susceptibility among mammalian species correlates with the toxin's metabolic patterns in brain microvessels and liver. JPET 244:443-448.

Riobo, N.A., E. Clementi, M. Melani, A. Boveris, E. Cadenas, S. Moncada, and J.J. Poderoso. 2001. Nitric oxide inhibits mitochondrial NADH: ubiquinone reductase activity through peroxynitrite formation. Biochem J 359:139-145.

Rollema, H., W.G. Kuhr, G. Kranenborg, J. De Vries, and C. Van den Berg. 1988. MPP+-induced efflux of dopamine and lactate from rat striatum have similar time courses as shown by in vivo brain dialysis. JPET 245:858-866.

Russ, H., K. Staust, F. Martel, M. Gliese, and E. Schomig. 1996. The extraneuronal transporter for monoamine transmitters exists in cells derived from human central nervous system glia. Eur J Neurosci 8: 1256-1264.

Saadat, S., A.D. Stehle, A. Lamouroux, J. Mallet, and H. Thoenen. 1988. Predicted amino acid sequence of bovine tyrosine hydroxylase and its similarity to tyrosine hydroxylases from other species. J Neurochem 51:572-578.

Schaar, D.G., B.A. Sieber, C.F. Dreyfus, and I.B. Black. 1993. Regional and cell-specific expression of GDNF in rat brain. Exp Neurol 124:368371.

Schaar, D.G., B.A. Sieber, A.C. Sherwood, D. Dean, G. Mendoza, L. Ramakrishnan, C.F. Dreyfus, and I.B. Black. 1994. Multiple astrocyte transcripts encode nigral trophic factors in rat and human. Exp Neurol 130:387-393.

Schabitz, W.R., C. Sommer, W. Zoder, M. Kiessling, M. Schwaninger, and S. Schwab. 2000. Intravenous brain-derived neurotrophic factor reduces infarct size and counterregulates Bax and Bcl-2 expression after temporary focal cerebral ischemia. Stroke 31:2212-2217.

Schipper, H.M. 1999. Glial HO-1 expression, iron deposition and oxidative stress in neurodegenerative diseases. Neurotox Res 1:57-70.

Schipper, H.M., A. Liberman, and E.G. Stopa. 1998a. Neural heme oxy-genase-1 expression in idiopathic Parkinson's disease. Exp Neurol 150:60-68.

Schipper, H.M., R. Vininsky, R. Brull, L. Small, and J.R. Brawer. 1998b. Astrocyte mitochondria: a substrate for iron deposition in the aging rat substantia nigra. Exp Neurol 152:188-196.

Schluter, O.M., F. Fornai, M.G. Alessandri, S. Takamori, M. Geppert, R. Jahn, and T.C. Sudhof. 2003. Role of alpha-synuclein in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in mice. Neurosci 118:985-1002.

Schmidt, C.J., L.A. Matsuda, and J.W. Gibb. 1984. In vitro release of tritiated monoamines from rat CNS tissue by the neurotoxic compound 1-methyl-phenyl-tetrahydropyridine. Eur J Pharm 103:255-260.

Schmidt, J., K. Mertz, and J.I. Morgan. 1999. Regulation of heme oxyge-nase-1 expression by dopamine in cultured C6 glioma and primary astrocytes. Mol Brain Res 73:50-59.

Schneider, J.S., and F.J. Denaro. 1988. Astrocytic responses to the do-paminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in cat and mouse brain. J Neuropath Exp Neurol 47:452458.

Schwarting, R.K., and J.P. Huston. 1996. The unilateral 6-hydroxydopamine lesion model in behavioral brain research. Analysis of functional deficits, recovery, and treatments. Prog Neurobiol 50: 275-331.

Scott, W.K., L.H. Yamaoka, J.M. Stajich, B.L. Scott, J.M. Vance, A.D. Roses, M.A. Pericak-Vance, R.L. Watts, M. Nance, J. Hubble, W. Koller, M.B. Stern, A. Colcher, F.H. Allen, Jr., B.C. Hiner, J. Jankovic, W. Ondo, N.G. Laing, F. Mastaglia, C. Goetz, E. Pappert, G.W. Small, D. Masterman, J.L. Haines, and T.L. Davies. 1999. The alpha-synuclein gene is not a major risk factor in familial Parkinson disease. Neuroge-netics 2:191-192.

Shults, C.W. 2003. Coenzyme Q10 in neurodegenerative diseases. Curr Med Chem 10:1917-1921.

Skaper, S.D., M. Floreani, A. Negro, L. Facci, and P. Giusti. 1998. Neurotrophins rescue cerebellar granule neurons from oxidative stress-mediated apoptotic death: selective involvement of phos-phatidylinositol 3-kinase and the mitogen-activated protein kinase pathway. J Neurochem 70:1859-1868.

Slivka, A., and G. Cohen. 1985. Hydroxyl radical attack on dopamine. J Biol Chem 260:15466-15472.

Smeyne, M., O. Goloubeva, and R.J. Smeyne. 2001. Strain-dependent susceptibility to MPTP and MPP+-induced Parkinsonism is determined by glia. Glia 74:73-80.

Sonsalla, P.K., and R.E. Heikkila. 1988. Neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine in several strains of mice. Prog Neuropsychopharmacol Biol Psychiatry 12:345-354.

Souza, J.M., B.I. Giasson, Q. Chen, V.M. Lee, and H. Ischiropoulos. 2000. Dityrosine cross-linking promotes formation of stable alpha-synuclein polymers. Implication of nitrative and oxidative stress in the pathogen-esis of neurodegenerative synucleinopathies. J Biol Chem 275:1834418349.

Spillantini, M.G., M.L. Schmidt, V.M. Lee, J.Q. Trojanowski, R. Jakes, and M. Goedert. 1997. Alpha-synuclein in Lewy bodies. Nature 388:839840.

Spina, M.B., S.P. Squinto, J. Miller, R.M. Lindsay, and C. Hyman. 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.

Stoessl, A.J. 1999. Etiology of Parkinson's disease. Can J Neurol Sci 26 Suppl 2:S5-12.

Sundstrom, E., I. Stromberg, T. Tsutsumi, L. Olson, and G. Jonsson. 1987. Studies on the effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on central catecholamine neurons in C57Bl/6 mice. Comparison with three other strains of mice. Brain Res 405:26-38.

Suzuki, K., Y. Mizuno, and M. Yoshida. 1990. Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-like compounds on mito-chondrial respiration. Adv Neurol 53:215-218.

Takahashi, N., L.L. Miner, I. Sora, H. Ujike, R.S. Revay, V. Kostic, V. Jackson-Lewis, S. Przedborski, and G.R. Uhl. 1997. VMAT2 knockout mice: heterozygotes display reduced amphetamine-conditioned reward, enhanced amphetamine locomotion, and enhanced MPTP toxicity. Proc Natl Acad Sci U S A 94:9938-9943.

Teismann, P., K. Tieu, O. Cohen, D.K. Choi, du C Wu, D. Marks, M. Vila, V. Jackson-Lewis, and S. Przedborski. 2003a. Pathogenic role of glial cells in Parkinson's disease. Mov Disord 18:121-129.

Teismann, P., K. Tieu, D.K. Choi, D.C. Wu, A. Naini, S. Hunot, M. Vila, V. Jackson-Lewis, and S. Przedborski. 2003b. Cyclooxygenase-2 is instrumental in Parkinson's disease neurodegeneration. Proc Natl Acad Sci U S A 100:5473-5478.

The Parkinsons Web. 1997. http://neuro-chief-e.mgh.harvard.edu:80/ parkinsonsweb/Main/pdmain.html#mainmenu.

Thiruchelvam, M., E.K. Richfield, R.B. Baggs, A.W. Tank, and D.A. Cory-Slechta. 2000. The nigrostriatal dopaminergic system as a preferential target of repeated exposures to combined paraquat and maneb: implications for Parkinson's disease. J Neurosci 20:9207-9214.

Tsukahara, T., M. Takeda, S. Shimohama, O. Ohara, and N. Hashimoto 1995. Effects of brain-derived neurotrophic factor on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in monkeys. Neurosurgery 37:733-739.

United States Census Bureau. 1996. Population Projections of the United States by Age, Sex, Race, and Hispanic Origin: 1993 to 2050.

Veldman, B.A., A.M. Wijn, N. Knoers, P. Praamstra, and M.W. Horstink 1998. Genetic and environmental risk factors in Parkinson's disease. Clin Neurol Neurosurg 100:15-26.

Walkinshaw, G., and C.M. Waters. 1995. Induction of apoptosis in cate-cholaminergic PC12 cells by L-dopa. Implications for the treatment of Parkinson's disease. J Clin Invest 95:2458-2464.

Wang, X.F., and M.S. Cynader. 2000. Astrocytes provide cysteine to neurons by releasing glutathione. J Neurochem 74:1434-1442.

Whetten-Goldstein, K., F. Sloan, E. Kulas, T. Cutson, and M. Schenkman. 1997. The burden of Parkinson's disease on society, family, and the individual. J Am Ger Soc 45:479-485.

Whone, A.L., R.L. Watts, A.J. Stoessl, M. Davis, S. Reske, C. Nahmias, A.E. Lang, O. Rascol, M.J. Ribeiro, P. Remy, W.H. Poewe, R.A. Hauser, and D.J. Brooks. 2003. Slower progression of Parkinson's disease with ropinirole versus levodopa: The REAL-PET study. Ann Neurol 54:93-101.

Wichmann, T., and M.R. DeLong. 2003. Pathophysiology of Parkinson's disease: the MPTP primate model of the human disorder. Ann N Y Acad Sci 991:199-213.

Williams, A.C., M.L. Smith, R.H. Waring, and D.B. Ramsden. 1999. Idio-pathic Parkinson's disease: a genetic and environmental model. Adv Neurol 80:215-218.

Wu, D.C., P. Teismann, K. Tieu, M. Vila, V. Jackson-Lewis, H. Ischiropoulos, and S. Przedborski. 2003. NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. Proc Natl Acad Sci U SA 100:6145-6150.

Wu, D.C., V. Jackson-Lewis, M. Vila, K. Tieu, P. Teismann, C. Vadseth, D.K. Choi, H. Ischiropoulos, and S. Przedborski. 2002. Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J Neu-rosci 22:1763-1771.

Youdim, M.B., E. Grunblatt, Y. Levites, G. Maor, and S. Mandel. 2002. Early and late molecular events in neurodegeneration and neuroprotection in Parkinson's disease MPTP model as assessed by cDNAmicroar-ray; the role of iron. Neurotox Res 4:679-689.

Zietlow, R., S.B. Dunnett, and J.W. Fawcett. 1999. The effect of microglia on embryonic dopaminergic neuronal survival in vitro: diffusible signals from neurons and glia change microglia from neurotoxic to neu-roprotective. Eur J Neurosci 11:1657-1667.

Was this article helpful?

0 0
All About Alzheimers

All About Alzheimers

The comprehensive new ebook All About Alzheimers puts everything into perspective. Youll gain insight and awareness into the disease. Learn how to maintain the patients emotional health. Discover tactics you can use to deal with constant life changes. Find out how counselors can help, and when they should intervene. Learn safety precautions that can protect you, your family and your loved one. All About Alzheimers will truly empower you.

Get My Free Ebook


Post a comment