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Arduini, Irene (2008) Toxic effects of the oxidized products of the neurotransmitter dopamine on mitochondria and their implications in Parkinson's disease. [Tesi di dottorato]

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Abstract (inglese)

Parkinson's disease (PD) is a chronic, progressive, neurodegenerative disorder clinically characterized by motor symptoms such as tremor at rest, rigidity, slowness of movement (bradykinesia), and postural instability.
One pathological hallmark of the disease is the progressive and striking loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). It is unclear why SNpc neurons die during PD. However, several biochemical hallmarks of the disease exist, and likely reveal clues to the underlying etiology of PD. Mitochondrial dysfunctions, at the level of complex I of the electronic transport chain (ETC), have been reported in the SNpc of PD patients. It has been hypothesized that the reason dopaminergic neurons of SNpc are vulnerable in PD is due to the toxic properties of the DA itself. DA is a highly reactive molecule, normally stored in synaptic vesicles. Increasing cytosolic dopamine in neurons and its oxidized metabolites has many deleterious effects, including increases in oxidative stress, mitochondrial dysfunction.The overall aim of the research that this dissertation comprises is to identify the mechanism that contributes to the selective degeneration of dopaminergic neurons in PD. The research described herein utilizes in vitro and cellular model approaches to test the hypothesis that the oxidized products of the neurotransmitter DA (DAQs) induce toxic effects on mitochondria. If this hypothesis is correct any pathological event that impairs DA synthesis, storage or metabolism, leading to the cytoplasmic accumulation of DA can increase the presence of oxidized products of DA and their toxic effects in the cell with mitochondria as one of the target. Mitochondrial dysfunctions derived from exposure to DA-oxidized products can account for the specific vulnerability of dopaminergic neurons and their degeneration in PD.

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Tipo di EPrint:Tesi di dottorato
Relatore:Bubacco, Luigi
Dottorato (corsi e scuole):Ciclo 20 > Corsi per il 20simo ciclo > FISIOLOGIA MOLECOLARE E BIOLOGIA STRUTTURALE
Data di deposito della tesi:Gennaio 2008
Anno di Pubblicazione:Gennaio 2008
Parole chiave (italiano / inglese):Parkinson's disease, dopamine, mitochondrial disfunction, dopamine quinones, oxidative stress
Settori scientifico-disciplinari MIUR:Area 05 - Scienze biologiche > BIO/10 Biochimica
Struttura di riferimento:Dipartimenti > Dipartimento di Biologia
Codice ID:761
Depositato il:23 Set 2008
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(1) Forno, L. S. (1996) Neuropathology of Parkinson's disease. J Neuropathol Exp Neurol 55, 259-72. Cerca con Google

(2) Pollanen, M. S., Dickson, D. W., and Bergeron, C. (1993) Pathology and biology of the Lewy body. J Neuropathol Exp Neurol 52, 183-91. Cerca con Google

(3) Schapira, A. H., Cooper, J. M., Dexter, D., Clark, J. B., Jenner, P., and Marsden, C. D. (1990) Mitochondrial complex I deficiency in Parkinson's disease. J Neurochem 54, 823-7. Cerca con Google

(4) Swerdlow, R. H., Parks, J. K., Miller, S. W., Tuttle, J. B., Trimmer, P. A., Sheehan, J. P., Bennett, J. P., Jr., Davis, R. E., and Parker, W. D., Jr. (1996) Origin and functional consequences of the complex I defect in Parkinson's disease. Ann Neurol 40, 663-71. Cerca con Google

(5) Dexter, D. T., Carter, C. J., Wells, F. R., Javoy-Agid, F., Agid, Y., Lees, A., Jenner, P., and Marsden, C. D. (1989) Basal lipid peroxidation in substantia nigra is increased in Parkinson's disease. J Neurochem 52, 381- 9. Cerca con Google

(6) Sofic, E., Riederer, P., Heinsen, H., Beckmann, H., Reynolds, G. P., Hebenstreit, G., and Youdim, M. B. (1988) Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain. J Neural Transm 74, 199-205. Cerca con Google

(7) Tatton, W. G., Chalmers-Redman, R., Brown, D., and Tatton, N. (2003) Apoptosis in Parkinson's disease: signals for neuronal degradation. Ann Neurol 53 Suppl 3, S61-70; discussion S70-2. Cerca con Google

(8) Vila, M., and Przedborski, S. (2003) Targeting programmed cell death in neurodegenerative diseases. Nat Rev Neurosci 4, 365-75. Cerca con Google

(9) Betarbet, R., Sherer, T. B., MacKenzie, G., Garcia-Osuna, M., Panov, A. V., and Greenamyre, J. T. (2000) Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci 3, 1301-6. Cerca con Google

(10) Langston, J. W., Ballard, P., Tetrud, J. W., and Irwin, I. (1983) Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219, 979-80. Cerca con Google

(11) Sherer, T. B., Betarbet, R., Testa, C. M., Seo, B. B., Richardson, J. R., Kim, J. H., Miller, G. W., Yagi, T., Matsuno-Yagi, A., and Greenamyre, J. T. (2003) Mechanism of toxicity in rotenone models of Parkinson's disease. J Neurosci 23, 10756-64. Cerca con Google

(12) Graham, D. G., Tiffany, S. M., Bell, W. R., Jr., and Gutknecht, W. F. (1978) Autoxidation versus covalent binding of quinones as the mechanism of toxicity of dopamine, 6-hydroxydopamine, and related compounds toward C1300 neuroblastoma cells in vitro. Mol Pharmacol 14, 644-53. Cerca con Google

(13) Lotharius, J., and Brundin, P. (2002) Pathogenesis of Parkinson's disease: dopamine, vesicles and alpha-synuclein. Nat Rev Neurosci 3, 932-42. Cerca con Google

(14) Sulzer, D., Bogulavsky, J., Larsen, K. E., Behr, G., Karatekin, E., Kleinman, M. H., Turro, N., Krantz, D., Edwards, R. H., Greene, L. A., and Zecca, L. (2000) Neuromelanin biosynthesis is driven by excess cytosolic catecholamines not accumulated by synaptic vesicles. Proc Natl Acad Sci U S A 97, 11869-74. Cerca con Google

(15) Betarbet, R., Sherer, T. B., and Greenamyre, J. T. (2002) Animal models of Parkinson's disease. Bioessays 24, 308-18. Cerca con Google

(16) Thyagarajan, D., Bressman, S., Bruno, C., Przedborski, S., Shanske, S., Lynch, T., Fahn, S., and DiMauro, S. (2000) A novel mitochondrial 12SrRNA point mutation in parkinsonism, deafness, and neuropathy. Ann Neurol 48, 730-6. Cerca con Google

(17) Simon, D. K., Pulst, S. M., Sutton, J. P., Browne, S. E., Beal, M. F., and Johns, D. R. (1999) Familial multisystem degeneration with parkinsonism associated with the 11778 mitochondrial DNA mutation. Neurology 53, 1787-93. Cerca con Google

(18) Luoma, P., Melberg, A., Rinne, J. O., Kaukonen, J. A., Nupponen, N. N., Chalmers, R. M., Oldfors, A., Rautakorpi, I., Peltonen, L., Majamaa, K., Somer, H., and Suomalainen, A. (2004) Parkinsonism, premature menopause, and mitochondrial DNA polymerase gamma mutations: clinical and molecular genetic study. Lancet 364, 875-82. Cerca con Google

(19) van der Walt, J. M., Nicodemus, K. K., Martin, E. R., Scott, W. K., Nance, M. A., Watts, R. L., Hubble, J. P., Haines, J. L., Koller, W. C., Lyons, K., Pahwa, R., Stern, M. B., Colcher, A., Hiner, B. C., Jankovic, J., Ondo, W. G., Allen, F. H., Jr., Goetz, C. G., Small, G. W., Mastaglia, F., Stajich, J. M., McLaurin, A. C., Middleton, L. T., Scott, B. L., Schmechel, D. E., Pericak-Vance, M. A., and Vance, J. M. (2003) Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease. Am J Hum Genet 72, 804-11. Cerca con Google

(20) Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y., and Shimizu, N. (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392, 605-8. Cerca con Google

(21) Darios, F., Corti, O., Lucking, C. B., Hampe, C., Muriel, M. P., Abbas, N., Gu, W. J., Hirsch, E. C., Rooney, T., Ruberg, M., and Brice, A. (2003) Parkin prevents mitochondrial swelling and cytochrome c release in mitochondria-dependent cell death. Hum Mol Genet 12, 517-26. Cerca con Google

(22) Kuroda, Y., Mitsui, T., Kunishige, M., Shono, M., Akaike, M., Azuma, H., and Matsumoto, T. (2006) Parkin enhances mitochondrial biogenesis in proliferating cells. Hum Mol Genet 15, 883-95. Cerca con Google

(23) Zhang, Y., Gao, J., Chung, K. K., Huang, H., Dawson, V. L., and Dawson, T. M. (2000) Parkin functions as an E2-dependent ubiquitin- protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1. Proc Natl Acad Sci U S A 97, 13354-9. Cerca con Google

(24) Shimura, H., Hattori, N., Kubo, S., Mizuno, Y., Asakawa, S., Minoshima, S., Shimizu, N., Iwai, K., Chiba, T., Tanaka, K., and Suzuki, T. (2000) Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet 25, 302-5. Cerca con Google

(25) Feany, M. B., and Pallanck, L. J. (2003) Parkin: a multipurpose neuroprotective agent? Neuron 38, 13-6. Cerca con Google

(26) Petrucelli, L., O'Farrell, C., Lockhart, P. J., Baptista, M., Kehoe, K., Vink, L., Choi, P., Wolozin, B., Farrer, M., Hardy, J., and Cookson, M. R. (2002) Parkin protects against the toxicity associated with mutant alphasynuclein: proteasome dysfunction selectively affects catecholaminergic neurons. Neuron 36, 1007-19. Cerca con Google

(27) Staropoli, J. F., McDermott, C., Martinat, C., Schulman, B., Demireva, E., and Abeliovich, A. (2003) Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity. Neuron 37, 735-49. Cerca con Google

(28) LaVoie, M. J., Ostaszewski, B. L., Weihofen, A., Schlossmacher, M. G., and Selkoe, D. J. (2005) Dopamine covalently modifies and functionally inactivates parkin. Nat Med 11, 1214-21. Cerca con Google

(29) Greene, J. C., Whitworth, A. J., Kuo, I., Andrews, L. A., Feany, M. B., and Pallanck, L. J. (2003) Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc Natl Acad Sci U S A 100, 4078-83. Cerca con Google

(30) Sang, T. K., Chang, H. Y., Lawless, G. M., Ratnaparkhi, A., Mee, L., Ackerson, L. C., Maidment, N. T., Krantz, D. E., and Jackson, G. R. (2007) A Drosophila model of mutant human parkin-induced toxicity demonstrates selective loss of dopaminergic neurons and dependence on cellular dopamine. J Neurosci 27, 981-92. Cerca con Google

(31) Goldberg, M. S., Fleming, S. M., Palacino, J. J., Cepeda, C., Lam, H. A., Bhatnagar, A., Meloni, E. G., Wu, N., Ackerson, L. C., Klapstein, G. J., Gajendiran, M., Roth, B. L., Chesselet, M. F., Maidment, N. T., Levine, M. S., and Shen, J. (2003) Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons. J Biol Chem 278, 43628-35. Cerca con Google

(32) Itier, J. M., Ibanez, P., Mena, M. A., Abbas, N., Cohen-Salmon, C., Bohme, G. A., Laville, M., Pratt, J., Corti, O., Pradier, L., Ret, G., Joubert, C., Periquet, M., Araujo, F., Negroni, J., Casarejos, M. J., Canals, S., Solano, R., Serrano, A., Gallego, E., Sanchez, M., Denefle, P., Benavides, J., Tremp, G., Rooney, T. A., Brice, A., and Garcia de Yebenes, J. (2003) Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse. Hum Mol Genet 12, 2277-91. Cerca con Google

(33) Perez, F. A., and Palmiter, R. D. (2005) Parkin-deficient mice are not a robust model of parkinsonism. Proc Natl Acad Sci U S A 102, 2174-9. Cerca con Google

(34) Bonifati, V., Rizzu, P., van Baren, M. J., Schaap, O., Breedveld, G. J., Krieger, E., Dekker, M. C., Squitieri, F., Ibanez, P., Joosse, M., van Dongen, J. W., Vanacore, N., van Swieten, J. C., Brice, A., Meco, G., van Duijn, C. M., Oostra, B. A., and Heutink, P. (2003) Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299, 256-9. Cerca con Google

(35) Bandopadhyay, R., Kingsbury, A. E., Cookson, M. R., Reid, A. R., Evans, I. M., Hope, A. D., Pittman, A. M., Lashley, T., Canet-Aviles, R., Miller, D. W., McLendon, C., Strand, C., Leonard, A. J., Abou-Sleiman, P. M., Healy, D. G., Ariga, H., Wood, N. W., de Silva, R., Revesz, T., Hardy, J. A., and Lees, A. J. (2004) The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson's disease. Brain 127, 420-30. Cerca con Google

(36) Canet-Aviles, R. M., Wilson, M. A., Miller, D. W., Ahmad, R., McLendon, C., Bandyopadhyay, S., Baptista, M. J., Ringe, D., Petsko, G. A., and Cookson, M. R. (2004) The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization. Proc Natl Acad Sci U S A 101, 9103-8. Cerca con Google

(37) Taira, T., Saito, Y., Niki, T., Iguchi-Ariga, S. M., Takahashi, K., and Ariga, H. (2004) DJ-1 has a role in antioxidative stress to prevent cell death. EMBO Rep 5, 213-8. Cerca con Google

(38) Chen, L., Cagniard, B., Mathews, T., Jones, S., Koh, H. C., Ding, Y., Carvey, P. M., Ling, Z., Kang, U. J., and Zhuang, X. (2005) Agedependent motor deficits and dopaminergic dysfunction in DJ-1 null mice. J Biol Chem 280, 21418-26. Cerca con Google

(39) Goldberg, M. S., Pisani, A., Haburcak, M., Vortherms, T. A., Kitada, T., Costa, C., Tong, Y., Martella, G., Tscherter, A., Martins, A., Bernardi, G., Roth, B. L., Pothos, E. N., Calabresi, P., and Shen, J. (2005) Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1. Neuron 45, 489-96. Cerca con Google

(40) Kim, R. H., Smith, P. D., Aleyasin, H., Hayley, S., Mount, M. P., Pownall, S., Wakeham, A., You-Ten, A. J., Kalia, S. K., Horne, P., Westaway, D., Lozano, A. M., Anisman, H., Park, D. S., and Mak, T. W. (2005) Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6- tetrahydropyrindine (MPTP) and oxidative stress. Proc Natl Acad Sci U S A 102, 5215-20. Cerca con Google

(41) Li, H. T., Lin, D. H., Luo, X. Y., Zhang, F., Ji, L. N., Du, H. N., Song, G. Q., Hu, J., Zhou, J. W., and Hu, H. Y. (2005) Inhibition of alpha-synuclein fibrillization by dopamine analogs via reaction with the amino groups of alpha-synuclein. Implication for dopaminergic neurodegeneration. Febs J 272, 3661-72. Cerca con Google

(42) Meulener, M. C., Xu, K., Thomson, L., Ischiropoulos, H., and Bonini, N. M. (2006) Mutational analysis of DJ-1 in Drosophila implicates functional inactivation by oxidative damage and aging. Proc Natl Acad Sci U S A 103, 12517-22. Cerca con Google

(43) Silvestri, L., Caputo, V., Bellacchio, E., Atorino, L., Dallapiccola, B., Valente, E. M., and Casari, G. (2005) Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism. Hum Mol Genet 14, 3477-92. Cerca con Google

(44) Petit, A., Kawarai, T., Paitel, E., Sanjo, N., Maj, M., Scheid, M., Chen, F., Gu, Y., Hasegawa, H., Salehi-Rad, S., Wang, L., Rogaeva, E., Fraser, P., Robinson, B., St George-Hyslop, P., and Tandon, A. (2005) Wild-type PINK1 prevents basal and induced neuronal apoptosis, a protective effect abrogated by Parkinson disease-related mutations. J Biol Chem 280, 34025-32. Cerca con Google

(45) Deng, H., Jankovic, J., Guo, Y., Xie, W., and Le, W. (2005) Small interfering RNA targeting the PINK1 induces apoptosis in dopaminergic cells SH-SY5Y. Biochem Biophys Res Commun 337, 1133-8. Cerca con Google

(46) Tang, B., Xiong, H., Sun, P., Zhang, Y., Wang, D., Hu, Z., Zhu, Z., Ma, H., Pan, Q., Xia, J. H., Xia, K., and Zhang, Z. (2006) Association of PINK1 and DJ-1 confers digenic inheritance of early-onset Parkinson's disease. Hum Mol Genet 15, 1816-25. Cerca con Google

(47) Yang, Y., Gehrke, S., Imai, Y., Huang, Z., Ouyang, Y., Wang, J. W., Yang, L., Beal, M. F., Vogel, H., and Lu, B. (2006) Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin. Proc Natl Acad Sci U S A 103, 10793-8. Cerca con Google

(48) Clark, I. E., Dodson, M. W., Jiang, C., Cao, J. H., Huh, J. R., Seol, J. H., Yoo, S. J., Hay, B. A., and Guo, M. (2006) Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441, 1162-6. Cerca con Google

(49) Park, J., Lee, S. B., Lee, S., Kim, Y., Song, S., Kim, S., Bae, E., Kim, J., Shong, M., Kim, J. M., and Chung, J. (2006) Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature 441, 1157- 61. Cerca con Google

(50) Plun-Favreau, H., Klupsch, K., Moisoi, N., Gandhi, S., Kjaer, S., Frith, D., Harvey, K., Deas, E., Harvey, R. J., McDonald, N., Wood, N. W., Martins, L. M., and Downward, J. (2007) The mitochondrial protease HtrA2 is regulated by Parkinson's disease-associated kinase PINK1. Nat Cell Biol 9, 1243-52. Cerca con Google

(51) Abeliovich, A., Schmitz, Y., Farinas, I., Choi-Lundberg, D., Ho, W. H., Castillo, P. E., Shinsky, N., Verdugo, J. M., Armanini, M., Ryan, A., Hynes, M., Phillips, H., Sulzer, D., and Rosenthal, A. (2000) Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25, 239-52. Cerca con Google

(52) Yavich, L., Jakala, P., and Tanila, H. (2006) Abnormal compartmentalization of norepinephrine in mouse dentate gyrus in alphasynuclein knockout and A30P transgenic mice. J Neurochem 99, 724-32. Cerca con Google

(53) Yavich, L., Tanila, H., Vepsalainen, S., and Jakala, P. (2004) Role of alpha-synuclein in presynaptic dopamine recruitment. J Neurosci 24, 11165-70. Cerca con Google

(54) Singleton, A. B., Farrer, M., Johnson, J., Singleton, A., Hague, S., Kachergus, J., Hulihan, M., Peuralinna, T., Dutra, A., Nussbaum, R., Lincoln, S., Crawley, A., Hanson, M., Maraganore, D., Adler, C., Cookson, M. R., Muenter, M., Baptista, M., Miller, D., Blancato, J., Hardy, J., and Gwinn-Hardy, K. (2003) alpha-Synuclein locus triplication causes Parkinson's disease. Science 302, 841. Cerca con Google

(55) 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. Nat Genet 18, 106-8. Cerca con Google

(56) 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, 2045-7. Cerca con Google

(57) Zarranz, J. J., Alegre, J., Gomez-Esteban, J. C., Lezcano, E., Ros, R., Ampuero, I., Vidal, L., Hoenicka, J., Rodriguez, O., Atares, B., Llorens, V., Gomez Tortosa, E., del Ser, T., Munoz, D. G., and de Yebenes, J. G. (2004) The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol 55, 164-73. Cerca con Google

(58) Spillantini, M. G., Crowther, R. A., Jakes, R., Hasegawa, M., and Goedert, M. (1998) alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with lewy bodies. Proc Natl Acad Sci U S A 95, 6469-73. Cerca con Google

(59) Bodner, R. A., Outeiro, T. F., Altmann, S., Maxwell, M. M., Cho, S. H., Hyman, B. T., McLean, P. J., Young, A. B., Housman, D. E., and Kazantsev, A. G. (2006) Pharmacological promotion of inclusion information: a therapeutic approach for Huntington's and Parkinson's diseases. Proc Natl Acad Sci U S A 103, 4246-51. Cerca con Google

(60) Cooper, A. A., Gitler, A. D., Cashikar, A., Haynes, C. M., Hill, K. J., Bhullar, B., Liu, K., Xu, K., Strathearn, K. E., Liu, F., Cao, S., Caldwell, K. A., Caldwell, G. A., Marsischky, G., Kolodner, R. D., Labaer, J., Rochet, J. C., Bonini, N. M., and Lindquist, S. (2006) Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models. Science 313, 324-8. Cerca con Google

(61) Song, D. D., Shults, C. W., Sisk, A., Rockenstein, E., and Masliah, E. (2004) Enhanced substantia nigra mitochondrial pathology in human alpha-synuclein transgenic mice after treatment with MPTP. Exp Neurol 186, 158-72. Cerca con Google

(62) Stichel, C. C., Zhu, X. R., Bader, V., Linnartz, B., Schmidt, S., and Lubbert, H. (2007) Mono- and double-mutant mouse models of Parkinson's disease display severe mitochondrial damage. Hum Mol Genet 16, 3377-93. Cerca con Google

(63) Klivenyi, P., Siwek, D., Gardian, G., Yang, L., Starkov, A., Cleren, C., Ferrante, R. J., Kowall, N. W., Abeliovich, A., and Beal, M. F. (2006) Mice lacking alpha-synuclein are resistant to mitochondrial toxins. Neurobiol Dis 21, 541-8. Cerca con Google

(64) Hasegawa, T., Matsuzaki-Kobayashi, M., Takeda, A., Sugeno, N., Kikuchi, A., Furukawa, K., Perry, G., Smith, M. A., and Itoyama, Y. (2006) Alpha-synuclein facilitates the toxicity of oxidized catechol metabolites: implications for selective neurodegeneration in Parkinson's disease. FEBS Lett 580, 2147-52. Cerca con Google

(65) Mosharov, E. V., Staal, R. G., Bove, J., Prou, D., Hananiya, A., Markov, D., Poulsen, N., Larsen, K. E., Moore, C. M., Troyer, M. D., Edwards, R. H., Przedborski, S., and Sulzer, D. (2006) Alpha-synuclein overexpression increases cytosolic catecholamine concentration. J Neurosci 26, 9304-11. Cerca con Google

(66) Paisan-Ruiz, C., Jain, S., Evans, E. W., Gilks, W. P., Simon, J., van der Brug, M., Lopez de Munain, A., Aparicio, S., Gil, A. M., Khan, N., Johnson, J., Martinez, J. R., Nicholl, D., Carrera, I. M., Pena, A. S., de Silva, R., Lees, A., Marti-Masso, J. F., Perez-Tur, J., Wood, N. W., and Singleton, A. B. (2004) Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 44, 595-600. Cerca con Google

(67) Zimprich, A., Biskup, S., Leitner, P., Lichtner, P., Farrer, M., Lincoln, S., Kachergus, J., Hulihan, M., Uitti, R. J., Calne, D. B., Stoessl, A. J., Pfeiffer, R. F., Patenge, N., Carbajal, I. C., Vieregge, P., Asmus, F., Muller-Myhsok, B., Dickson, D. W., Meitinger, T., Strom, T. M., Wszolek, Z. K., and Gasser, T. (2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44, 601-7. Cerca con Google

(68) Di Fonzo, A., Rohe, C. F., Ferreira, J., Chien, H. F., Vacca, L., Stocchi, F., Guedes, L., Fabrizio, E., Manfredi, M., Vanacore, N., Goldwurm, S., Breedveld, G., Sampaio, C., Meco, G., Barbosa, E., Oostra, B. A., and Bonifati, V. (2005) A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson's disease. Lancet 365, 412-5. Cerca con Google

(69) Gilks, W. P., Abou-Sleiman, P. M., Gandhi, S., Jain, S., Singleton, A., Lees, A. J., Shaw, K., Bhatia, K. P., Bonifati, V., Quinn, N. P., Lynch, J., Healy, D. G., Holton, J. L., Revesz, T., and Wood, N. W. (2005) A common LRRK2 mutation in idiopathic Parkinson's disease. Lancet 365, 415-6. Cerca con Google

(70) Nichols, W. C., Pankratz, N., Hernandez, D., Paisan-Ruiz, C., Jain, S., Halter, C. A., Michaels, V. E., Reed, T., Rudolph, A., Shults, C. W., Singleton, A., and Foroud, T. (2005) Genetic screening for a single common LRRK2 mutation in familial Parkinson's disease. Lancet 365, 410-2. Cerca con Google

(71) Greggio, E., Jain, S., Kingsbury, A., Bandopadhyay, R., Lewis, P., Kaganovich, A., van der Brug, M. P., Beilina, A., Blackinton, J., Thomas, K. J., Ahmad, R., Miller, D. W., Kesavapany, S., Singleton, A., Lees, A., Harvey, R. J., Harvey, K., and Cookson, M. R. (2006) Kinase activity is required for the toxic effects of mutant LRRK2/dardarin. Neurobiol Dis 23, 329-41 Cerca con Google

(72) Greggio, E., Lewis, P. A., van der Brug, M. P., Ahmad, R., Kaganovich, A., Ding, J., Beilina, A., Baker, A. K., and Cookson, M. R. (2007) Mutations in LRRK2/dardarin associated with Parkinson disease are more toxic than equivalent mutations in the homologous kinase LRRK1. J Neurochem 102, 93-102. Cerca con Google

(73) Lewis, P. A., Greggio, E., Beilina, A., Jain, S., Baker, A., and Cookson, M. R. (2007) The R1441C mutation of LRRK2 disrupts GTP hydrolysis. Biochem Biophys Res Commun 357, 668-71. Cerca con Google

(74) Kumer, S. C., and Vrana, K. E. (1996) Intricate regulation of tyrosine hydroxylase activity and gene expression. J Neurochem 67, 443-62. Cerca con Google

(75) Haavik, J., Le Bourdelles, B., Martinez, A., Flatmark, T., and Mallet, J. (1991) Recombinant human tyrosine hydroxylase isozymes. Reconstitution with iron and inhibitory effect of other metal ions. Eur J Biochem 199, 371-8. Cerca con Google

(76) Kilty, J. E., Lorang, D., and Amara, S. G. (1991) Cloning and expression of a cocaine-sensitive rat dopamine transporter. Science 254, 578-9. Cerca con Google

(77) Sulzer, D., and Zecca, L. (2000) Intraneuronal dopamine-quinone synthesis: a review. Neurotox Res 1, 181-95. Cerca con Google

(78) Burke, W. J., Li, S. W., Chung, H. D., Ruggiero, D. A., Kristal, B. S., Johnson, E. M., Lampe, P., Kumar, V. B., Franko, M., Williams, E. A., and Zahm, D. S. (2004) Neurotoxicity of MAO metabolites of catecholamine neurotransmitters: role in neurodegenerative diseases. Neurotoxicology 25, 101-15. Cerca con Google

(79) Halliwell, B. (1992) Reactive oxygen species and the central nervous system. J Neurochem 59, 1609-23. Cerca con Google

(80) Youdim, M. B. (1988) Iron in the brain: implications for Parkinson's and Alzheimer's diseases. Mt Sinai J Med 55, 97-101. Cerca con Google

(81) Bisaglia, M., Mammi, S., and Bubacco, L. (2007) in J Biol Chem pp 15597-605. Cerca con Google

(82) Greggio, E., Bergantino, E., Carter, D., Ahmad, R., Costin, G. E., Hearing, V. J., Clarimon, J., Singleton, A., Eerola, J., Hellstrom, O., Tienari, P. J., Miller, D. W., Beilina, A., Bubacco, L., and Cookson, M. R. (2005) Tyrosinase exacerbates dopamine toxicity but is not genetically associated with Parkinson's disease. J Neurochem 93, 246-56. Cerca con Google

(83) Hastings, T. G. (1995) Enzymatic oxidation of dopamine: the role of prostaglandin H synthase. J Neurochem 64, 919-24. Cerca con Google

(84) Blarzino, C., Mosca, L., Foppoli, C., Coccia, R., De Marco, C., and Rosei, M. A. (1999) Lipoxygenase/H2O2-catalyzed oxidation of dihdroxyindoles: synthesis of melanin pigments and study of their antioxidant properties. Free Radic Biol Med 26, 446-53. Cerca con Google

(85) Fornstedt, B. (1990) Role of catechol autooxidation in the degeneration of dopamine neurons. Acta Neurol Scand Suppl 129, 12-4. Cerca con Google

(86) Tse, D. C., McCreery, R. L., and Adams, R. N. (1976) Potential oxidative pathways of brain catecholamines. J Med Chem 19, 37-40. Cerca con Google

(87) Jenner, P. (2003) Oxidative stress in Parkinson's disease. Ann Neurol 53 Suppl 3, S26-36; discussion S36-8. Cerca con Google

(88) Spencer, J. P., Jenner, P., Daniel, S. E., Lees, A. J., Marsden, D. C., and Halliwell, B. (1998) Conjugates of catecholamines with cysteine and GSH in Parkinson's disease: possible mechanisms of formation involving reactive oxygen species. J Neurochem 71, 2112-22. Cerca con Google

(89) Li, H., and Dryhurst, G. (1997) Irreversible inhibition of mitochondrial complex I by 7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4- benzothiazine-3-carboxyli c acid (DHBT-1): a putative nigral endotoxin of relevance to Parkinson's disease. J Neurochem 69, 1530-41. Cerca con Google

(90) Zhang, F., and Dryhurst, G. (1994) Effects of L-cysteine on the oxidation chemistry of dopamine: new reaction pathways of potential relevance to idiopathic Parkinson's disease. J Med Chem 37, 1084- 98. Cerca con Google

(91) Graham, D. G. (1978) Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol 14, 633- 43. Cerca con Google

(92) LaVoie, 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, 1484-91. Cerca con Google

(93) Xu, Y., Stokes, A. H., Roskoski, R., Jr., and Vrana, K. E. (1998) Dopamine, in the presence of tyrosinase, covalently modifies and inactivates tyrosine hydroxylase. J Neurosci Res 54, 691-7. Cerca con Google

(94) Whitehead, R. E., Ferrer, J. V., Javitch, J. A., and Justice, J. B. (2001) Reaction of oxidized dopamine with endogenous cysteine residues in the human dopamine transporter. J Neurochem 76, 1242-51. 100 Cerca con Google

(95) Berman, S. B., and Hastings, T. G. (1997) Inhibition of glutamate transport in synaptosomes by dopamine oxidation and reactive oxygen species. J Neurochem 69, 1185-95. Cerca con Google

(96) Stokes, A. H., Hastings, T. G., and Vrana, K. E. (1999) Cytotoxic and genotoxic potential of dopamine. J Neurosci Res 55, 659-65. Cerca con Google

(97) Conway, K. A., Rochet, J. C., Bieganski, R. M., and Lansbury, P. T., Jr. (2001) Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct. Science 294, 1346-9. Cerca con Google

(98) Zoccarato, F., Cavallini, L., and Alexandre, A. (2004) Respirationdependent removal of exogenous H2O2 in brain mitochondria: inhibition by Ca2+. J Biol Chem 279, 4166-74. Cerca con Google

(99) Costantini, P., Petronilli, V., Colonna, R., and Bernardi, P. (1995) On the effects of paraquat on isolated mitochondria. Evidence that paraquat causes opening of the cyclosporin A-sensitive permeability transition pore synergistically with nitric oxide. Toxicology 99, 77-88. Cerca con Google

(100) Janssen, A. J., Trijbels, F. J., Sengers, R. C., Smeitink, J. A., van den Heuvel, L. P., Wintjes, L. T., Stoltenborg-Hogenkamp, B. J., and Rodenburg, R. J. (2007) Spectrophotometric assay for complex I of the respiratory chain in tissue samples and cultured fibroblasts. Clin Chem 53, 729-34. Cerca con Google

(101) Laemmli, U. K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680-5. Cerca con Google

(102) Zerbetto, E., Vergani, L., and Dabbeni-Sala, F. (1997) Quantification of muscle mitochondrial oxidative phosphorylation enzymes via histochemical staining of blue native polyacrylamide gels. Electrophoresis 18, 2059-64. Cerca con Google

(103) Hirsch, E., Graybiel, A. M., and Agid, Y. A. (1988) Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease. Nature 334, 345-8. Cerca con Google

(104) Erickson, J. D., Eiden, L. E., and Hoffman, B. J. (1992) Expression cloning of a reserpine-sensitive vesicular monoamine transporter. Proc Natl Acad Sci U S A 89, 10993-7. Cerca con Google

(105) Liu, Y., Peter, D., Roghani, A., Schuldiner, S., Prive, G. G., Eisenberg, D., Brecha, N., and Edwards, R. H. (1992) A cDNA that suppresses MPP+ toxicity encodes a vesicular amine transporter. Cell 70, 539-51. Cerca con Google

(106) Hastings, T. G., Lewis, D. A., and Zigmond, M. J. (1996) Reactive dopamine metabolites and neurotoxicity: implications for Parkinson's disease. Adv Exp Med Biol 387, 97-106. Cerca con Google

(107) Ito, S., Kato, T., and Fujita, K. (1988) Covalent binding of catechols to proteins through the sulphydryl group. Biochem Pharmacol 37, 1707-10. Cerca con Google

(108) Kuhn, D. M., Arthur, R. E., Jr., Thomas, D. M., and Elferink, L. A. (1999) Tyrosine hydroxylase is inactivated by catechol-quinones and converted to a redox-cycling quinoprotein: possible relevance to Parkinson's disease. J Neurochem 73, 1309-17. Cerca con Google

(109) Spencer, J. P., Whiteman, M., Jenner, P., and Halliwell, B. (2002) 5-s- Cysteinyl-conjugates of catecholamines induce cell damage, extensive DNA base modification and increases in caspase-3 activity in neurons. J Neurochem 81, 122-9. Cerca con Google

(110) Berman, S. B., and Hastings, T. G. (1999) Dopamine oxidation alters mitochondrial respiration and induces permeability transition in brain mitochondria: implications for Parkinson's disease. J Neurochem 73, 1127- 37. Cerca con Google

(111) Brenner-Lavie, H., Klein, E., Zuk, R., Gazawi, H., Ljubuncic, P., and Ben- Shachar, D. (2007) Dopamine modulates mitochondrial function in viable SH-SY5Y cells possibly via its interaction with complex I: Relevance to dopamine pathology in schizophrenia. Biochim Biophys Acta. Cerca con Google

(112) Jana, S., Maiti, A. K., Bagh, M. B., Banerjee, K., Das, A., Roy, A., and Chakrabarti, S. (2007) Dopamine but not 3,4-dihydroxy phenylacetic acid (DOPAC) inhibits brain respiratory chain activity by autoxidation and mitochondria catalyzed oxidation to quinone products: implications in Parkinson's disease. Brain Res 1139, 195-200. Cerca con Google

(113) Zoccarato, F., Toscano, P., and Alexandre, A. (2005) Dopamine-derived dopaminochrome promotes H(2)O(2) release at mitochondrial complex I: stimulation by rotenone, control by Ca(2+), and relevance to Parkinson disease. J Biol Chem 280, 15587-94. Cerca con Google

(114) Ben-Shachar, D., Zuk, R., Gazawi, H., and Ljubuncic, P. (2004) Dopamine toxicity involves mitochondrial complex I inhibition: implications to dopamine-related neuropsychiatric disorders. Biochem Pharmacol 67, 1965-74. Cerca con Google

(115) Khan, F. H., Sen, T., Maiti, A. K., Jana, S., Chatterjee, U., and Chakrabarti, S. (2005) Inhibition of rat brain mitochondrial electron transport chain activity by dopamine oxidation products during extended in vitro incubation: implications for Parkinson's disease. Biochim Biophys Acta 1741, 65-74. Cerca con Google

(116) Cabezon, E., Runswick, M. J., Leslie, A. G., and Walker, J. E. (2001) The structure of bovine IF(1), the regulatory subunit of mitochondrial FATPase. Embo J 20, 6990-6. Cerca con Google

(117) Greenamyre, J. T., Sherer, T. B., Betarbet, R., and Panov, A. V. (2001) Complex I and Parkinson's disease. IUBMB Life 52, 135-41. Cerca con Google

(118) Bernardi, P., and Forte, M. (2007) The mitochondrial permeability transition pore. Novartis Found Symp 287, 157-64; discussion 164-9. Cerca con Google

(119) Bernardi, P., Krauskopf, A., Basso, E., Petronilli, V., Blachly-Dyson, E., Di Lisa, F., and Forte, M. A. (2006) The mitochondrial permeability transition from in vitro artifact to disease target. Febs J 273, 2077-99. Cerca con Google

(120) Forte, M., and Bernardi, P. (2005) Genetic dissection of the permeability transition pore. J Bioenerg Biomembr 37, 121-8. Cerca con Google

(121) Bernardi, P., Petronilli, V., Di Lisa, F., and Forte, M. (2001) A mitochondrial perspective on cell death. Trends Biochem Sci 26, 112-7. Cerca con Google

(122) Crompton, M. (1999) The mitochondrial permeability transition pore and its role in cell death. Biochem J 341 ( Pt 2), 233-49. Cerca con Google

(123) Crompton, M., Virji, S., Doyle, V., Johnson, N., and Ward, J. M. (1999) The mitochondrial permeability transition pore. Biochem Soc Symp 66, 167-79. Cerca con Google

(124) Forte, M., and Bernardi, P. (2006) The permeability transition and BCL-2 family proteins in apoptosis: co-conspirators or independent agents? Cell Death Differ 13, 1287-90. Cerca con Google

(125) Haworth, R. A., and Hunter, D. R. (1979) The Ca2+-induced membrane transition in mitochondria. II. Nature of the Ca2+ trigger site. Arch Biochem Biophys 195, 460-7. Cerca con Google

(126) Bernardi, P., Colonna, R., Costantini, P., Eriksson, O., Fontaine, E., Ichas, F., Massari, S., Nicolli, A., Petronilli, V., and Scorrano, L. (1998) The mitochondrial permeability transition. Biofactors 8, 273-81. Cerca con Google

(127) Petronilli, V., Cola, C., Massari, S., Colonna, R., and Bernardi, P. (1993) Physiological effectors modify voltage sensing by the cyclosporin Asensitive permeability transition pore of mitochondria. J Biol Chem 268, 21939-45. Cerca con Google

(128) Costantini, P., Chernyak, B. V., Petronilli, V., and Bernardi, P. (1996) Modulation of the mitochondrial permeability transition pore by pyridine nucleotides and dithiol oxidation at two separate sites. J Biol Chem 271, 6746-51. Cerca con Google

(129) Chernyak, B. V., and Bernardi, P. (1996) The mitochondrial permeability transition pore is modulated by oxidative agents through both pyridine nucleotides and glutathione at two separate sites. Eur J Biochem 238, 623- 30. Cerca con Google

(130) Hatefi, Y. (1985) The mitochondrial electron transport and oxidative phosphorylation system. Annu Rev Biochem 54, 1015-69. Cerca con Google

(131) Fontaine, E., Eriksson, O., Ichas, F., and Bernardi, P. (1998) Regulation of the permeability transition pore in skeletal muscle mitochondria. Modulation By electron flow through the respiratory chain complex i. J Biol Chem 273, 12662-8. Cerca con Google

(132) Chauvin, C., De Oliveira, F., Ronot, X., Mousseau, M., Leverve, X., and Fontaine, E. (2001) Rotenone inhibits the mitochondrial permeability transition-induced cell death in U937 and KB cells. J Biol Chem 276, 41394-8. Cerca con Google

(133) Huang, G., Lu, H., Hao, A., Ng, D. C., Ponniah, S., Guo, K., Lufei, C., Zeng, Q., and Cao, X. (2004) GRIM-19, a cell death regulatory protein, is essential for assembly and function of mitochondrial complex I. Mol Cell Biol 24, 8447-56. Cerca con Google

(134) Robinson, B. H. (1998) Human complex I deficiency: clinical spectrum and involvement of oxygen free radicals in the pathogenicity of the defect. Biochim Biophys Acta 1364, 271-86. Cerca con Google

(135) Haas, R. H., Nasirian, F., Nakano, K., Ward, D., Pay, M., Hill, R., and Shults, C. W. (1995) Low platelet mitochondrial complex I and complex II/III activity in early untreated Parkinson's disease. Ann Neurol 37, 714- 22. Cerca con Google

(136) Krige, D., Carroll, M. T., Cooper, J. M., Marsden, C. D., and Schapira, A. H. (1992) Platelet mitochondrial function in Parkinson's disease. The Royal Kings and Queens Parkinson Disease Research Group. Ann Neurol 32, 782-8. Cerca con Google

(137) Parker, W. D., Jr., Boyson, S. J., and Parks, J. K. (1989) Abnormalities of the electron transport chain in idiopathic Parkinson's disease. Ann Neurol 26, 719-23. Cerca con Google

(138) Yoshino, H., Nakagawa-Hattori, Y., Kondo, T., and Mizuno, Y. (1992) Mitochondrial complex I and II activities of lymphocytes and platelets in Parkinson's disease. J Neural Transm Park Dis Dement Sect 4, 27-34. Cerca con Google

(139) Gu, M., Cooper, J. M., Taanman, J. W., and Schapira, A. H. (1998) Mitochondrial DNA transmission of the mitochondrial defect in Parkinson's disease. Ann Neurol 44, 177-86. Cerca con Google

(140) Marella, M., Seo, B. B., Nakamaru-Ogiso, E., Greenamyre, J. T., Matsuno-Yagi, A., and Yagi, T. (2008) Protection by the NDI1 Gene against Neurodegeneration in a Rotenone Rat Model of Parkinson's Disease. PLoS ONE 3, e1433. Cerca con Google

(141) Seo, B. B., Nakamaru-Ogiso, E., Flotte, T. R., Matsuno-Yagi, A., and Yagi, T. (2006) In vivo complementation of complex I by the yeast Ndi1 enzyme. Possible application for treatment of Parkinson disease. J Biol Chem 281, 14250-5. Cerca con Google

(142) Asanuma, M., Miyazaki, I., and Ogawa, N. (2003) Dopamine- or LDOPA- induced neurotoxicity: the role of dopamine quinone formation and tyrosinase in a model of Parkinson's disease. Neurotox Res 5, 165-76. Cerca con Google

(143) Sulzer, D. (2007) Multiple hit hypotheses for dopamine neuron loss in Parkinson's disease. Trends Neurosci 30, 244-50. Cerca con Google

(144) Ribeiro, M. J., Vidailhet, M., Loc'h, C., Dupel, C., Nguyen, J. P., Ponchant, M., Dolle, F., Peschanski, M., Hantraye, P., Cesaro, P., Samson, Y., and Remy, P. (2002) Dopaminergic function and dopamine transporter binding assessed with positron emission tomography in Parkinson disease. Arch Neurol 59, 580-6. Cerca con Google

(145) Sossi, V., de La Fuente-Fernandez, R., Holden, J. E., Doudet, D. J., McKenzie, J., Stoessl, A. J., and Ruth, T. J. (2002) Increase in dopamine turnover occurs early in Parkinson's disease: evidence from a new modeling approach to PET 18 F-fluorodopa data. J Cereb Blood Flow Metab 22, 232-9. Cerca con Google

(146) Lotharius, J., and Brundin, P. (2002) Impaired dopamine storage resulting from alpha-synuclein mutations may contribute to the pathogenesis of Parkinson's disease. Hum Mol Genet 11, 2395-407. Cerca con Google

(147) Dauer, W., and Przedborski, S. (2003) Parkinson's disease: mechanisms and models. Neuron 39, 889-909. Cerca con Google

(148) Paumard, P., Vaillier, J., Coulary, B., Schaeffer, J., Soubannier, V., Mueller, D. M., Brethes, D., di Rago, J. P., and Velours, J. (2002) The ATP synthase is involved in generating mitochondrial cristae morphology. Embo J 21, 221-30. Cerca con Google

(149) Barrio, J. R., Huang, S. C., Melega, W. P., Yu, D. C., Hoffman, J. M., Schneider, J. S., Satyamurthy, N., Mazziotta, J. C., and Phelps, M. E. (1990) 6-[18F]fluoro-L-dopa probes dopamine turnover rates in central dopaminergic structures. J Neurosci Res 27, 487-93. Cerca con Google

(150) Murphy, M. P. (2001) Development of lipophilic cations as therapies for disorders due to mitochondrial dysfunction. Expert Opin Biol Ther 1, 753- 64. Cerca con Google

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