Table of Contents Author Guidelines Submit a Manuscript
Oxidative Medicine and Cellular Longevity
Volume 2012, Article ID 624925, 25 pages
http://dx.doi.org/10.1155/2012/624925
Review Article

Oxidative Stress in Genetic Mouse Models of Parkinson’s Disease

Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Center for Neurosciences, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium

Received 24 February 2012; Revised 12 April 2012; Accepted 12 April 2012

Academic Editor: Krzysztof Ksiazek

Copyright © 2012 Mustafa Varçin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. A. Obeso, M. C. Rodriguez-Oroz, C. G. Goetz et al., “Missing pieces in the Parkinson's disease puzzle,” Nature Medicine, vol. 16, no. 6, pp. 653–661, 2010. View at Google Scholar
  2. D. Crosiers, J. Theuns, P. Cras, and C. Van Broeckhoven, “Parkinson disease: insights in clinical, genetic and pathological features of monogenic disease subtypes,” Journal of Chemical Neuroanatomy, vol. 42, no. 2, pp. 131–141, 2011. View at Publisher · View at Google Scholar · View at Scopus
  3. C. Sundal, S. Fujioka, R. J. Uitti, and Z. K. Wszolek, “Autosomal dominant Parkinson's disease,” Parkinsonism & Related Disorders, vol. 18, supplement 1, pp. S7–S10, 2012. View at Google Scholar
  4. H. Reichmann, “View point: etiology in Parkinson's disease. Dual hit or spreading intoxication,” Journal of the Neurological Sciences, vol. 310, no. 1-2, pp. 9–11, 2011. View at Publisher · View at Google Scholar · View at Scopus
  5. S. Lesage and A. Brice, “Role of Mendelian genes in “sporadic” Parkinson's disease,” Parkinsonism & Related Disorders, vol. 18, supplement 1, pp. S66–S70, 2012. View at Google Scholar
  6. C. Taccioli, V. Maselli, J. Tegnér et al., “ParkDB: a Parkinson's disease gene expression database,” Database, vol. 2011, article bar007, 2011. View at Publisher · View at Google Scholar
  7. J. M. Shulman, P. L. De Jager, and M. B. Feany, “Parkinson's disease: genetics and pathogenesis,” Annual Review of Pathology, vol. 6, pp. 193–222, 2011. View at Publisher · View at Google Scholar · View at Scopus
  8. C. J. Dunning et al., “Can Parkinson's disease pathology be propagated from one neuron to another?” Progress in Neurobiology. In press.
  9. C. Henchcliffe and F. M. Beal, “Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis,” Nature Clinical Practice Neurology, vol. 4, no. 11, pp. 600–609, 2008. View at Publisher · View at Google Scholar · View at Scopus
  10. H. Braak, K. Del Tredici, U. Rüb, R. A. I. De Vos, E. N. H. Jansen Steur, and E. Braak, “Staging of brain pathology related to sporadic Parkinson's disease,” Neurobiology of Aging, vol. 24, no. 2, pp. 197–211, 2003. View at Publisher · View at Google Scholar · View at Scopus
  11. C. H. Hawkes, K. Del Tredici, and H. Braak, “A timeline for Parkinson's disease,” Parkinsonism and Related Disorders, vol. 16, no. 2, pp. 79–84, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. A. H. V. Schapira, “Neurobiology and treatment of Parkinson's disease,” Trends in Pharmacological Sciences, vol. 30, no. 1, pp. 41–47, 2009. View at Publisher · View at Google Scholar · View at Scopus
  13. F. Stocchi and C. W. Olanow, “Neuroprotection in Parkinson's disease: clinical trials,” Annals of Neurology, vol. 53, no. 3, supplement, pp. S87–S99, 2003. View at Publisher · View at Google Scholar · View at Scopus
  14. T. A. Yacoubian and D. G. Standaert, “Targets for neuroprotection in Parkinson's disease,” Biochimica et Biophysica Acta, vol. 1792, no. 7, pp. 676–687, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. D. Blum, S. Torch, N. Lambeng et al., “Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson's disease,” Progress in Neurobiology, vol. 65, no. 2, pp. 135–172, 2001. View at Publisher · View at Google Scholar · View at Scopus
  16. K. Aoyama, M. Watabe, and T. Nakaki, “Regulation of neuronal glutathione synthesis,” Journal of Pharmacological Sciences, vol. 108, no. 3, pp. 227–238, 2008. View at Publisher · View at Google Scholar · View at Scopus
  17. P. Jenner, “Oxidative stress in Parkinson's disease,” Annals of Neurology, vol. 53, supplement 3, pp. S26–S36, 2003. View at Google Scholar
  18. S. Kawajiri, S. Saiki, S. Sato, and N. Hattori, “Genetic mutations and functions of PINK1,” Trends in Pharmacological Sciences, vol. 32, no. 10, pp. 573–580, 2011. View at Google Scholar
  19. R. C. S. Seet, C. Y. J. Lee, E. C. H. Lim et al., “Oxidative damage in Parkinson disease: measurement using accurate biomarkers,” Free Radical Biology and Medicine, vol. 48, no. 4, pp. 560–566, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. P. Jenner, “Oxidative mechanisms in nigral cell death in Parkinson's disease,” Movement Disorders, vol. 13, no. 1, pp. 24–34, 1998. View at Google Scholar · View at Scopus
  21. M. P. Smith and W. A. Cass, “Oxidative stress and dopamine depletion in an intrastriatal 6-hydroxydopamine model of Parkinson's disease,” Neuroscience, vol. 144, no. 3, pp. 1057–1066, 2007. View at Publisher · View at Google Scholar · View at Scopus
  22. T. M. Dawson, H. S. Ko, and V. L. Dawson, “Genetic animal models of Parkinson's disease,” Neuron, vol. 66, no. 5, pp. 646–661, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. M. J. Farrer, “Genetics of Parkinson disease: paradigm shifts and future prospects,” Nature Reviews Genetics, vol. 7, no. 4, pp. 306–318, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. M. P. Horowitz and J. T. Greenamyre, “Gene-environment interactions in parkinson's disease: the importance of animal modeling,” Clinical Pharmacology and Therapeutics, vol. 88, no. 4, pp. 467–474, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. K. J. Thomas and M. R. Cookson, “The role of PTEN-induced kinase 1 in mitochondrial dysfunction and dynamics,” International Journal of Biochemistry and Cell Biology, vol. 41, no. 10, pp. 2025–2035, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. D. J. Moore, A. B. West, V. L. Dawson, and T. M. Dawson, “Molecular pathophysiology of Parkinson's disease,” Annual Review of Neuroscience, vol. 28, pp. 57–87, 2005. View at Publisher · View at Google Scholar · View at Scopus
  27. R. S. Akundi, L. Zhi, and H. Bueler, “PINK1 enhances insulin-like growth factor-1-dependent Akt signaling and protection against apoptosis,” Neurobiology of Disease, vol. 45, no. 1, pp. 469–478, 2011. View at Google Scholar
  28. M. Diedrich, T. Kitada, G. Nebrich et al., “Brain region specific mitophagy capacity could contribute to selective neuronal vulnerability in Parkinson's disease,” Proteome Science, vol. 9, p. 59, 2011. View at Google Scholar
  29. C. A. Gautier, T. Kitada, and J. Shen, “Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 32, pp. 11364–11369, 2008. View at Publisher · View at Google Scholar · View at Scopus
  30. E. Deas, H. Plun-Faureau, and N. W. Wood, “PINK1 function in health and disease,” EMBO Molecular Medicine, vol. 1, no. 3, pp. 152–165, 2009. View at Publisher · View at Google Scholar · View at Scopus
  31. I. Dalle-Donne, D. Giustarini, R. Colombo, R. Rossi, and A. Milzani, “Protein carbonylation in human diseases,” Trends in Molecular Medicine, vol. 9, no. 4, pp. 169–176, 2003. View at Publisher · View at Google Scholar · View at Scopus
  32. A. Toulouse and A. M. Sullivan, “Progress in Parkinson's disease-Where do we stand?” Progress in Neurobiology, vol. 85, no. 4, pp. 376–392, 2008. View at Publisher · View at Google Scholar · View at Scopus
  33. K. Cui, X. Luo, K. Xu, and M. R. Ven Murthy, “Role of oxidative stress in neurodegeneration: recent developments in assay methods for oxidative stress and nutraceutical antioxidants,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 28, no. 5, pp. 771–799, 2004. View at Publisher · View at Google Scholar · View at Scopus
  34. Y. Gilgun-Sherki, E. Melamed, and D. Offen, “Oxidative stress induced-neurodegenerative diseases: the need for antioxidants that penetrate the blood brain barrier,” Neuropharmacology, vol. 40, no. 8, pp. 959–975, 2001. View at Publisher · View at Google Scholar · View at Scopus
  35. R. B. Mythri, C. Venkateshappa, G. Harish et al., “Evaluation of Markers of oxidative stress, antioxidant function and astrocytic proliferation in the striatum and frontal cortex of Parkinson's disease brains,” Neurochemical Research, vol. 36, no. 8, pp. 1452–1463, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. J. K. Andersen, “Oxidative stress in neurodegeneration: cause or consequence?” Nature Medicine, vol. 10, pp. S18–S25, 2004. View at Google Scholar · View at Scopus
  37. H. E. de Vries, M. Witte, D. Hondius et al., “Nrf2-induced antioxidant protection: a promising target to counteract ROS-mediated damage in neurodegenerative disease?” Free Radical Biology and Medicine, vol. 45, no. 10, pp. 1375–1383, 2008. View at Publisher · View at Google Scholar · View at Scopus
  38. S. Fahn and G. Cohen, “The oxidant stress hypothesis in Parkinson's disease: evidence supporting it,” Annals of Neurology, vol. 32, no. 6, pp. 804–812, 1992. View at Publisher · View at Google Scholar · View at Scopus
  39. M. B. Youdim, N. Drigues, and S. Mandel, “Oxidative stress indices in Parkinson's disease: biochemical determination,” Methods in Molecular Medicine, vol. 62, pp. 137–153, 2001. View at Google Scholar
  40. T. Ilic, M. Jovanović, A. Jovicić, and M. Tomović, “Oxidative stress and Parkinson's disease,” Vojnosanitetski Pregled, vol. 55, no. 5, pp. 463–468, 1998. View at Google Scholar
  41. M. Vinish, A. Anand, and S. Prabhakar, “Altered oxidative stress levels in Indian Parkinson's disease patients with PARK2 mutations,” Acta Biochimica Polonica, vol. 58, no. 2, pp. 165–169, 2011. View at Google Scholar · View at Scopus
  42. M. L. Selley, “(E)-4-Hydroxy-2-nonenal may be involved in the pathogenesis of Parkinson's disease,” Free Radical Biology and Medicine, vol. 25, no. 2, pp. 169–174, 1998. View at Publisher · View at Google Scholar · View at Scopus
  43. C. Buhmann, S. Arlt, A. Kontush et al., “Plasma and CSF markers of oxidative stress are increased in Parkinson's disease and influenced by antiparkinsonian medication,” Neurobiology of Disease, vol. 15, no. 1, pp. 160–170, 2004. View at Publisher · View at Google Scholar · View at Scopus
  44. P. del Hoyo, A. García-Redondo, F. de Bustos et al., “Oxidative stress in skin fibroblasts cultures from patients with Parkinson's disease,” BMC Neurology, vol. 10, p. 95, 2011. View at Google Scholar
  45. B. Byers, B. Cord, H. N. Nguyen et al., “SNCA triplication Parkinson's patient's iPSC-derived DA neurons accumulate alpha-synuclein and are susceptible to oxidative stress,” PLoS ONE, vol. 6, no. 11, Article ID e26159, 2011. View at Google Scholar
  46. F. P. Bellinger, M. T. Bellinger, L. A. Seale et al., “Glutathione peroxidase 4 is associated with neuromelanin in substantia nigra and dystrophic axons in putamen of Parkinson's brain,” Molecular Neurodegeneration, vol. 6, no. 1, article 8, 2011. View at Publisher · View at Google Scholar · View at Scopus
  47. L. Migliore and F. Coppedè, “Environmental-induced oxidative stress in neurodegenerative disorders and aging,” Mutation Research, vol. 674, no. 1-2, pp. 73–84, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. T. Müller and S. Muhlack, “Cysteinyl-glycine reduction as marker for levodopa-induced oxidative stress in Parkinson's disease patients,” Movement Disorders, vol. 26, no. 3, pp. 543–546, 2011. View at Publisher · View at Google Scholar · View at Scopus
  49. T. Müller, C. Jugel, R. Ehret et al., “Elevation of total homocysteine levels in patients with Parkinson's disease treated with duodenal levodopa/carbidopa gel,” Journal of Neural Transmission, vol. 118, no. 9, pp. 1329–1333, 2011. View at Publisher · View at Google Scholar · View at Scopus
  50. A. H. V. Schapira, “Present and future drug treatment for Parkinson's disease,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 76, no. 11, pp. 1472–1478, 2005. View at Publisher · View at Google Scholar · View at Scopus
  51. K. J. Barnham, C. L. Masters, and A. I. Bush, “Neurodegenerative diseases and oxidatives stress,” Nature Reviews Drug Discovery, vol. 3, no. 3, pp. 205–214, 2004. View at Google Scholar · View at Scopus
  52. C. Mytilineou, B. C. Kramer, and J. A. Yabut, “Glutathione depletion and oxidative stress,” Parkinsonism and Related Disorders, vol. 8, no. 6, pp. 385–387, 2002. View at Publisher · View at Google Scholar · View at Scopus
  53. R. A. Roberts, R. A. Smith, S. Safe, C. Szabo, R. B. Tjalkens, and F. M. Robertson, “Toxicological and pathophysiological roles of reactive oxygen and nitrogen species,” Toxicology, vol. 276, no. 2, pp. 85–94, 2010. View at Publisher · View at Google Scholar · View at Scopus
  54. G. Stefanoni, G. Sala, and L. Tremolizzo, “Alpha-synuclein, oxidative stress and autophagy failure: dangerous liaisons in dopaminergic neurodegeneration,” in Etiology and Pathophysiology of Parkinson's Disease, A. Q. Rana, Ed., InTech, 2011. View at Google Scholar
  55. D. M. Crabtree and J. Zhang, “Genetically engineered mouse models of Parkinson's disease,” Brain Research Bulletin. In press.
  56. J. Lotharius and P. Brundin, “Pathogenesis of Parkinson's disease: dopamine, vesicles and alpha-synuclein,” Nature reviews. Neuroscience, vol. 3, no. 12, pp. 932–942, 2002. View at Google Scholar · View at Scopus
  57. A. H. Schapira, “Mitochondrial pathology in Parkinson's disease,” Mount Sinai Journal of Medicine, vol. 78, no. 6, pp. 872–881, 2011. View at Google Scholar
  58. A. H. V. Schapira and M. Gegg, “Mitochondrial contribution to parkinson's disease pathogenesis,” Parkinson's Disease, vol. 2011, Article ID 159160, 7 pages, 2011. View at Publisher · View at Google Scholar · View at Scopus
  59. R. K. Chaturvedi and M. F. Beal, “Mitochondrial approaches for neuroprotection,” Annals of the New York Academy of Sciences, vol. 1147, pp. 395–412, 2008. View at Publisher · View at Google Scholar · View at Scopus
  60. R. H. Swerdlow, J. K. Parks, S. W. Miller et al., “Origin and functional consequences of the complex I defect in Parkinson's disease,” Annals of Neurology, vol. 40, no. 4, pp. 663–671, 1996. View at Google Scholar
  61. S. Fulda, L. Galluzzi, and G. Kroemer, “Targeting mitochondria for cancer therapy,” Nature Reviews Drug Discovery, vol. 9, no. 6, pp. 447–464, 2010. View at Publisher · View at Google Scholar · View at Scopus
  62. M. Dumont and M. F. Beal, “Neuroprotective strategies involving ROS in Alzheimer disease,” Free Radical Biology and Medicine, vol. 51, no. 5, pp. 1014–1026, 2011. View at Publisher · View at Google Scholar · View at Scopus
  63. P. M. Abou-Sleiman, M. M. K. Muqit, and N. W. Wood, “Expanding insights of mitochondrial dysfunction in Parkinson's disease,” Nature Reviews Neuroscience, vol. 7, no. 3, pp. 207–219, 2006. View at Publisher · View at Google Scholar · View at Scopus
  64. J. A. Petko, N. Kabbani, C. Frey et al., “Proteomic and functional analysis of NCS-1 binding proteins reveals novel signaling pathways required for inner ear development in zebrafish,” BMC Neuroscience, vol. 10, article 27, 2009. View at Publisher · View at Google Scholar · View at Scopus
  65. S. Gandhi, A. Wood-Kaczmar, Z. Yao et al., “PINK1-associated Parkinson's disease is caused by neuronal vulnerability to calcium-induced cell death,” Molecular Cell, vol. 33, no. 5, pp. 627–638, 2009. View at Publisher · View at Google Scholar · View at Scopus
  66. M. L. Block, L. Zecca, and J. S. Hong, “Microglia-mediated neurotoxicity: uncovering the molecular mechanisms,” Nature Reviews Neuroscience, vol. 8, no. 1, pp. 57–69, 2007. View at Publisher · View at Google Scholar · View at Scopus
  67. A. G. Ceulemans, T. Zgavc, R. Kooijman, S. Hachimi-Idrissi, S. Sarre, and Y. Michotte, “The dual role of the neuroinflammatory response after ischemic stroke: modulatory effects of hypothermia,” Journal of Neuroinflammation, vol. 7, article 74, 2010. View at Publisher · View at Google Scholar · View at Scopus
  68. C. Chéret, A. Gervais, A. Lelli et al., “Neurotoxic activation of microglia is promoted by a Nox1-dependent NADPH oxidase,” Journal of Neuroscience, vol. 28, no. 46, pp. 12039–12051, 2008. View at Publisher · View at Google Scholar · View at Scopus
  69. P. S. Whitton, “Inflammation as a causative factor in the aetiology of Parkinson's disease,” British Journal of Pharmacology, vol. 150, no. 8, pp. 963–976, 2007. View at Publisher · View at Google Scholar · View at Scopus
  70. C. M. Long-Smith, A. M. Sullivan, and Y. M. Nolan, “The influence of microglia on the pathogenesis of Parkinson's disease,” Progress in Neurobiology, vol. 89, no. 3, pp. 277–287, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. L. Qian, P. M. Flood, and J. S. Hong, “Neuroinflammation is a key player in Parkinson's disease and a prime target for therapy,” Journal of Neural Transmission, vol. 117, no. 8, pp. 971–979, 2010. View at Publisher · View at Google Scholar · View at Scopus
  72. J. S. Beckman, T. W. Beckman, J. Chen, P. A. Marshall, and B. A. Freeman, “Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide,” Proceedings of the National Academy of Sciences of the United States of America, vol. 87, no. 4, pp. 1620–1624, 1990. View at Google Scholar · View at Scopus
  73. T. Münzel and J. F. Keaney, “Are ACE inhibitors a “magic bullet” against oxidative stress?” Circulation, vol. 104, no. 13, pp. 1571–1574, 2001. View at Google Scholar · View at Scopus
  74. V. Anantharam, S. Kaul, C. Song, A. Kanthasamy, and A. G. Kanthasamy, “Pharmacological inhibition of neuronal NADPH oxidase protects against 1-methyl-4-phenylpyridinium (MPP+)-induced oxidative stress and apoptosis in mesencephalic dopaminergic neuronal cells,” NeuroToxicology, vol. 28, no. 5, pp. 988–997, 2007. View at Publisher · View at Google Scholar · View at Scopus
  75. B. Mertens, P. Vanderheyden, Y. Michotte, and S. Sarre, “The role of the central renin-angiotensin system in Parkinson's disease,” Journal of the Renin-Angiotensin-Aldosterone System, vol. 11, no. 1, pp. 49–56, 2010. View at Publisher · View at Google Scholar · View at Scopus
  76. B. Mertens, M. Varcin, Y. Michotte, and S. Sarre, “The neuroprotective action of candesartan is related to interference with the early stages of 6-hydroxydopamine-induced dopaminergic cell death,” European Journal of Neuroscience, vol. 34, no. 7, pp. 1141–1148, 2011. View at Google Scholar
  77. V. H. Perry, J. A. R. Nicoll, and C. Holmes, “Microglia in neurodegenerative disease,” Nature Reviews Neurology, vol. 6, no. 4, pp. 193–201, 2010. View at Publisher · View at Google Scholar · View at Scopus
  78. T. M. Dawson and V. L. Dawson, “Molecular pathways of neurodegeneration in Parkinson's disease,” Science, vol. 302, no. 5646, pp. 819–822, 2003. View at Publisher · View at Google Scholar · View at Scopus
  79. K. J. A. Davies, “Oxidative stress, antioxidant defenses, and damage removal, repair, and replacement systems,” IUBMB Life, vol. 50, no. 4-5, pp. 279–289, 2000. View at Publisher · View at Google Scholar · View at Scopus
  80. T. Finkel and N. J. Holbrook, “Oxidants, oxidative stress and the biology of ageing,” Nature, vol. 408, no. 6809, pp. 239–247, 2000. View at Publisher · View at Google Scholar · View at Scopus
  81. J. Clark and D. K. Simon, “Transcribe to survive: transcriptional control of antioxidant defense programs for neuroprotection in parkinson's disease,” Antioxidants and Redox Signaling, vol. 11, no. 3, pp. 509–528, 2009. View at Publisher · View at Google Scholar · View at Scopus
  82. J. G. Scandalios, “Oxidative stress: molecular perception and transduction of signals triggering antioxidant gene defenses,” Brazilian Journal of Medical and Biological Research, vol. 38, no. 7, pp. 995–1014, 2005. View at Google Scholar · View at Scopus
  83. V. Calabrese, E. Guagliano, M. Sapienza et al., “Redox regulation of cellular stress response in aging and neurodegenerative disorders: role of vitagenes,” Neurochemical Research, vol. 32, no. 4-5, pp. 757–773, 2007. View at Publisher · View at Google Scholar · View at Scopus
  84. G. Twig, A. Elorza, A. J. A. Molina et al., “Fission and selective fusion govern mitochondrial segregation and elimination by autophagy,” EMBO Journal, vol. 27, no. 2, pp. 433–446, 2008. View at Publisher · View at Google Scholar · View at Scopus
  85. T. Tatsuta and T. Langer, “Quality control of mitochondria: protection against neurodegeneration and ageing,” EMBO Journal, vol. 27, no. 2, pp. 306–314, 2008. View at Publisher · View at Google Scholar · View at Scopus
  86. C. Vives-Bauza and S. Przedborski, “Mitophagy: the latest problem for Parkinson's disease,” Trends in Molecular Medicine, vol. 17, no. 3, pp. 158–165, 2011. View at Publisher · View at Google Scholar · View at Scopus
  87. R. J. Youle and D. P. Narendra, “Mechanisms of mitophagy,” Nature Reviews Molecular Cell Biology, vol. 12, no. 1, pp. 9–14, 2011. View at Publisher · View at Google Scholar · View at Scopus
  88. M. F. Beal, “Parkinson's disease: a model dilemma,” Nature, vol. 466, no. 7310, pp. S8–S10, 2010. View at Publisher · View at Google Scholar · View at Scopus
  89. H. L. Melrose, S. J. Lincoln, G. M. Tyndall, and M. J. Farrer, “Parkinson's disease: a rethink of rodent models,” Experimental Brain Research, vol. 173, no. 2, pp. 196–204, 2006. View at Publisher · View at Google Scholar · View at Scopus
  90. S. Duty and P. Jenner, “Animal models of Parkinson's disease: a source of novel treatments and clues to the cause of the disease,” British Journal of Pharmacology, vol. 164, no. 4, pp. 1357–1391, 2011. View at Google Scholar
  91. M. A. Gama Sosa, R. de Gasperi, and G. A. Elder, “Modeling human neurodegenerative diseases in transgenic systems,” Human Genetics, vol. 131, no. 4, pp. 535–563, 2012. View at Google Scholar
  92. C. Fernandes and Y. Rao, “Genome-wide screen for modifiers of Parkinson's disease genes in Drosophila,” Molecular Brain, vol. 4, no. 1, article 17, 2011. View at Publisher · View at Google Scholar · View at Scopus
  93. L. Chen, B. Cagniard, T. Mathews et al., “Age-dependent motor deficits and dopaminergic dysfunction in DJ-1 null mice,” Journal of Biological Chemistry, vol. 280, no. 22, pp. 21418–21426, 2005. View at Publisher · View at Google Scholar · View at Scopus
  94. E. Andres-Mateos, C. Perier, L. Zhang et al., “DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 37, pp. 14807–14812, 2007. View at Publisher · View at Google Scholar · View at Scopus
  95. H. Yamaguchi and J. Shen, “Absence of dopaminergic neuronal degeneration and oxidative damage in aged DJ-I-deficient mice,” Molecular Neurodegeneration, vol. 2, no. 1, article 10, 2007. View at Publisher · View at Google Scholar · View at Scopus
  96. J. N. Guzman, J. Sanchez-Padilla, D. Wokosin et al., “Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1,” Nature, vol. 468, no. 7324, pp. 696–700, 2010. View at Publisher · View at Google Scholar · View at Scopus
  97. I. Irrcher, H. Aleyasin, E. L. Seifert et al., “Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics,” Human Molecular Genetics, vol. 19, no. 19, pp. 3734–3746, 2010. View at Google Scholar
  98. F. A. Perez, W. R. Curtis, and R. D. Palmiter, “Parkin-deficient mice are not more sensitive to 6-hydroxydopamine or methamphetamine neurotoxicity,” BMC Neuroscience, vol. 6, article 71, 2005. View at Publisher · View at Google Scholar · View at Scopus
  99. J. M. Itier, P. Ibáñez, M. A. Mena et al., “Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse,” Human Molecular Genetics, vol. 12, no. 18, pp. 2277–2291, 2003. View at Publisher · View at Google Scholar · View at Scopus
  100. J. J. Palacino, D. Sagi, M. S. Goldberg et al., “Mitochondrial dysfunction and oxidative damage in parkin-deficient mice,” Journal of Biological Chemistry, vol. 279, no. 18, pp. 18614–18622, 2004. View at Publisher · View at Google Scholar · View at Scopus
  101. M. Periquet, O. Corti, S. Jacquier, and A. Brice, “Proteomic analysis of parkin knockout mice: alterations in energy metabolism, protein handling and synaptic function,” Journal of Neurochemistry, vol. 95, no. 5, pp. 1259–1276, 2005. View at Publisher · View at Google Scholar · View at Scopus
  102. J. A. Rodríguez-Navarro, M. J. Casarejos, J. Menéndez et al., “Mortality, oxidative stress and tau accumulation during ageing in parkin null mice,” Journal of Neurochemistry, vol. 103, no. 1, pp. 98–114, 2007. View at Publisher · View at Google Scholar · View at Scopus
  103. X. H. Lu, S. M. Fleming, B. Meurers et al., “Bacterial artificial chromosome transgenic mice expressing a truncated mutant parkin exhibit age-dependent hypokinetic motor deficits, dopaminergic neuron degeneration, and accumulation of proteinase k-resistant α-Synuclein,” Journal of Neuroscience, vol. 29, no. 7, pp. 1962–1976, 2009. View at Publisher · View at Google Scholar · View at Scopus
  104. R. S. Akundi, Z. Huang, J. Eason et al., “Increased mitochondrial calcium sensitivity and abnormal expression of innate immunity genes precede dopaminergic defects in Pink1-deficient mice,” PLoS ONE, vol. 6, no. 1, Article ID e16038, 2011. View at Publisher · View at Google Scholar · View at Scopus
  105. F. Billia, L. Hauck, F. Konecny, V. Rao, J. Shen, and T. W. Mak, “PTEN-inducible kinase 1 (PINK1)/Park6 is indispensable for normal heart function,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 23, pp. 9572–9577, 2011. View at Publisher · View at Google Scholar · View at Scopus
  106. P. Klivenyi, D. Siwek, G. Gardian et al., “Mice lacking alpha-synuclein are resistant to mitochondrial toxins,” Neurobiology of Disease, vol. 21, no. 3, pp. 541–548, 2006. View at Publisher · View at Google Scholar · View at Scopus
  107. M. Neumann, P. J. Kahle, B. I. Giasson et al., “Misfolded proteinase K-resistant hyperphosphorylated α-synuclein in aged transgenic mice with locomotor deterioration and in human α-synucleinopathies,” Journal of Clinical Investigation, vol. 110, no. 10, pp. 1429–1439, 2002. View at Publisher · View at Google Scholar · View at Scopus
  108. H. F. Poon, M. Frasier, N. Shreve, V. Calabrese, B. Wolozin, and D. A. Butterfield, “Mitochondrial associated metabolic proteins are selectively oxidized in A30P α-synuclein transgenic mice—a model of familial Parkinson's disease,” Neurobiology of Disease, vol. 18, no. 3, pp. 492–498, 2005. View at Publisher · View at Google Scholar · View at Scopus
  109. B. I. Giasson, J. E. Duda, S. M. Quinn, B. Zhang, J. Q. Trojanowski, and V. M. Y. Lee, “Neuronal α-synucleinopathy with severe movement disorder in mice expressing A53T human α-synuclein,” Neuron, vol. 34, no. 4, pp. 521–533, 2002. View at Publisher · View at Google Scholar · View at Scopus
  110. L. J. Martin, Y. Pan, A. C. Price et al., “Parkinson's disease α-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death,” Journal of Neuroscience, vol. 26, no. 1, pp. 41–50, 2006. View at Publisher · View at Google Scholar · View at Scopus
  111. R. M. Miller, G. L. Kiser, T. Kaysser-Kranich et al., “Wild-type and mutant α-synuclein induce a multi-component gene expression profile consistent with shared pathophysiology in different transgenic mouse models of PD,” Experimental Neurology, vol. 204, no. 1, pp. 421–432, 2007. View at Publisher · View at Google Scholar · View at Scopus
  112. A. O. Koob, K. Ubhi, J. F. Paulsson et al., “Lovastatin ameliorates α-synuclein accumulation and oxidation in transgenic mouse models of α-synucleinopathies,” Experimental Neurology, vol. 221, no. 2, pp. 267–274, 2010. View at Publisher · View at Google Scholar · View at Scopus
  113. K. A. Brandis, I. F. Holmes, S. J. England, N. Sharma, L. Kukreja, and S. K. DebBurman, “α-synuclein fission yeast model: concentration-dependent aggregation without plasma membrane localization or toxicity,” Journal of Molecular Neuroscience, vol. 28, no. 2, pp. 179–192, 2006. View at Publisher · View at Google Scholar · View at Scopus
  114. F. A. Perez and R. D. Palmiter, “Parkin-deficient mice are not a robust model of parkinsonism,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 6, pp. 2174–2179, 2005. View at Publisher · View at Google Scholar · View at Scopus
  115. T. Kitada, A. Pisani, M. Karouani et al., “Impaired dopamine release and synaptic plasticity in the striatum of Parkin-/- mice,” Journal of Neurochemistry, vol. 110, no. 2, pp. 613–621, 2009. View at Publisher · View at Google Scholar · View at Scopus
  116. J. H. Son, H. Kawamata, M. S. Yoo et al., “Neurotoxicity and behavioral deficits associated with Septin 5 accumulation in dopaminergic neurons,” Journal of Neurochemistry, vol. 94, no. 4, pp. 1040–1053, 2005. View at Publisher · View at Google Scholar · View at Scopus
  117. S. Sato, T. Chiba, S. Nishiyama et al., “Decline of striatal dopamine release in parkin-deficient mice shown by ex vivo autoradiography,” Journal of Neuroscience Research, vol. 84, no. 6, pp. 1350–1357, 2006. View at Publisher · View at Google Scholar · View at Scopus
  118. R. Von Coelln, B. Thomas, J. M. Savitt et al., “Loss of locus coeruleus neurons and reduced startle in parkin null mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 29, pp. 10744–10749, 2004. View at Publisher · View at Google Scholar · View at Scopus
  119. X. Wang, D. Winter, G. Ashrafi et al., “PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility,” Cell, vol. 147, no. 4, pp. 893–906, 2011. View at Google Scholar
  120. V. A. Morais, P. Verstreken, A. Roethig et al., “Parkinson's disease mutations in PINK1 result in decreased Complex I activity and deficient synaptic function,” EMBO Molecular Medicine, vol. 1, no. 2, pp. 99–111, 2009. View at Publisher · View at Google Scholar · View at Scopus
  121. T. Kitada, A. Pisani, D. R. Porter et al., “Impaired dopamine release and synaptic plasticity in the striatum of PINK1-deficient mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 27, pp. 11441–11446, 2007. View at Publisher · View at Google Scholar · View at Scopus
  122. S. Gispert, F. Ricciardi, A. Kurz et al., “Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration,” PLoS ONE, vol. 4, no. 6, Article ID e5777, 2009. View at Publisher · View at Google Scholar · View at Scopus
  123. H. Zhou, B. H. Falkenburger, J. B. Schulz, K. Tieu, Z. Xu, and G. X. Xu, “Silencing of the Pink1 gene expression by conditional RNAi does not induce dopaminergic neuron death in mice,” International Journal of Biological Sciences, vol. 3, no. 4, pp. 242–250, 2007. View at Google Scholar · View at Scopus
  124. R. D. Mills, C. H. Sim, S. S. Mok, T. D. Mulhern, J. G. Culvenor, and H. C. Cheng, “Biochemical aspects of the neuroprotective mechanism of PTEN-induced kinase-1 (PINK1),” Journal of Neurochemistry, vol. 105, no. 1, pp. 18–33, 2008. View at Publisher · View at Google Scholar · View at Scopus
  125. A. Wood-Kaczmar, S. Gandhi, Z. Yao et al., “PINK1 is necessary for long term survival and mitochondrial function in human dopaminergic neurons,” PLoS ONE, vol. 3, no. 6, Article ID e2455, 2008. View at Publisher · View at Google Scholar · View at Scopus
  126. M. E. Gegg, J. M. Cooper, A. H. V. Schapira, and J. W. Taanman, “Silencing of PINK1 expression affects mitochondrial DNA and oxidative phosphorylation in DOPAMINERGIC cells,” PLoS ONE, vol. 4, no. 3, Article ID e4756, 2009. View at Publisher · View at Google Scholar · View at Scopus
  127. N. Kabbani, L. Negyessy, R. Lin, P. Goldman-Rakic, and R. Levenson, “Interaction with neuronal calcium sensor NCS-1 mediates desensitization of the D2 dopamine receptor,” Journal of Neuroscience, vol. 22, no. 19, pp. 8476–8486, 2002. View at Google Scholar · View at Scopus
  128. O. Pongs, J. Lindemeier, X. R. Zhu et al., “Frequenin—a novel calcium-binding protein that modulates synaptic efficacy in the Drosophila nervous system,” Neuron, vol. 11, no. 1, pp. 15–28, 1993. View at Publisher · View at Google Scholar · View at Scopus
  129. T. Hatano, S. I. Kubo, S. Sato, and N. Hattori, “Pathogenesis of familial Parkinson's disease: new insights based on monogenic forms of Parkinson's disease,” Journal of Neurochemistry, vol. 111, no. 5, pp. 1075–1093, 2009. View at Publisher · View at Google Scholar · View at Scopus
  130. J. H. Pogson, R. M. Ivatt, and A. J. Whitworth, “Molecular mechanisms of PINK1-related neurodegeneration,” Current Neurology and Neuroscience Reports, vol. 11, no. 3, pp. 283–290, 2011. View at Publisher · View at Google Scholar · View at Scopus
  131. A. Pilsl and K. F. Winklhofer, “Parkin, PINK1 and mitochondrial integrity: emerging concepts of mitochondrial dysfunction in Parkinson's disease,” Acta Neuropathologica, vol. 2, pp. 173–188, 2012. View at Google Scholar
  132. D. P. Narendra, S. M. Jin, A. Tanaka et al., “PINK1 is selectively stabilized on impaired mitochondria to activate Parkin,” PLoS Biology, vol. 8, no. 1, Article ID e1000298, 2010. View at Publisher · View at Google Scholar · View at Scopus
  133. T. Kitada, Y. Tong, C. A. Gautier, and J. Shen, “Absence of nigral degeneration in aged parkin/DJ-1/PINK1 triple knockout mice,” Journal of Neurochemistry, vol. 111, no. 3, pp. 696–702, 2009. View at Publisher · View at Google Scholar · View at Scopus
  134. J. A. Klein and S. L. Ackerman, “Oxidative stress, cell cycle, and neurodegeneration,” Journal of Clinical Investigation, vol. 111, no. 6, pp. 785–793, 2003. View at Publisher · View at Google Scholar · View at Scopus
  135. T. Hatano and N. Hattori, “Etiology and pathogenesis of Parkinson’s disease,” in Etiology and Pathophysiology of Parkinson's Disease, A. Q. Rana, Ed., InTech, 2011. View at Google Scholar
  136. A. R. Chade, M. Kasten, and C. M. Tanner, “Nongenetic causes of Parkinson's disease,” Journal of Neural Transmission, no. 70, supplement, pp. 147–151, 2006. View at Google Scholar · View at Scopus
  137. S. C. Marques, C. R. Oliveira, C. M. Pereira, and T. F. Outeiro, “Epigenetics in neurodegeneration: a new layer of complexity,” Progress in Neuro-Psychopharmacology & Biological Psychiatry, vol. 35, no. 2, pp. 348–355, 2011. View at Google Scholar
  138. O. Babenko, I. Kovalchuk, and G. A. Metz, “Epigenetic programming of neurodegenerative diseases by an adverse environment,” Brain Research, vol. 1444, pp. 96–111, 2012. View at Google Scholar
  139. F. Blandini, M. T. Armentero, and E. Martignoni, “The 6-hydroxydopamine model: news from the past,” Parkinsonism and Related Disorders, vol. 14, no. 2, pp. S124–S129, 2008. View at Publisher · View at Google Scholar · View at Scopus
  140. R. H. Kim, P. D. Smith, H. Aleyasin et al., “Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6- tetrahydropyrindine (MPTP) and oxidative stress,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 14, pp. 5215–5220, 2005. View at Publisher · View at Google Scholar · View at Scopus
  141. A. B. Manning-Bog et al., “Increased vulnerability of nigrostriatal terminals in DJ-1-deficient mice is mediated by the dopamine transporter,” Neurobiology of Disease, vol. 27, no. 2, pp. 141–150, 2007. View at Google Scholar
  142. J. C. Paterna, A. Leng, E. Weber, J. Feldon, and H. Büeler, “DJ-1 and parkin modulate dopamine-dependent behavior and inhibit MPTP-induced nigral dopamine neuron loss in mice,” Molecular Therapy, vol. 15, no. 4, pp. 698–704, 2007. View at Publisher · View at Google Scholar · View at Scopus
  143. H. Zhou, C. Huang, J. Tong, and X. G. Xia, “Early exposure to paraquat sensitizes dopaminergic neurons to subsequent silencing of PINK1 gene expression in mice,” International Journal of Biological Sciences, vol. 7, no. 8, pp. 1180–1187, 2011. View at Google Scholar
  144. M. E. Haque, K. J. Thomas, C. D'Souza et al., “Cytoplasmic Pink1 activity protects neurons from dopaminergic neurotoxin MPTP,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 5, pp. 1716–1721, 2008. View at Publisher · View at Google Scholar · View at Scopus
  145. W. Dauer, N. Kholodilov, M. Vila et al., “Resistance of α-synuclein null mice to the parkinsonian neurotoxin MPTP,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 22, pp. 14524–14529, 2002. View at Publisher · View at Google Scholar · View at Scopus
  146. O. M. Schlüter, F. Fornai, M. G. Alessandrí et al., “Role of α-synuclein in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism in mice,” Neuroscience, vol. 118, no. 4, pp. 985–1002, 2003. View at Publisher · View at Google Scholar · View at Scopus
  147. R. E. Drolet, B. Behrouz, K. J. Lookingland, and J. L. Goudreau, “Mice lacking α-synuclein have an attenuated loss of striatal dopamine following prolonged chronic MPTP administration,” NeuroToxicology, vol. 25, no. 5, pp. 761–769, 2004. View at Publisher · View at Google Scholar · View at Scopus
  148. D. C. Robertson, O. Schmidt, N. Ninkina, P. A. Jones, J. Sharkey, and V. L. Buchman, “Developmental loss and resistance to MPTP toxicity of dopaminergic neurones in substantia nigra pars compacta of γ-synuclein, α-synuclein and double α/γ-synuclein null mutant mice,” Journal of Neurochemistry, vol. 89, no. 5, pp. 1126–1136, 2004. View at Publisher · View at Google Scholar · View at Scopus
  149. F. Fornai, O. M. Schlüter, P. Lenzi et al., “Parkinson-like syndrome induced by continuous MPTP infusion: convergent roles of the ubiquitin-proteasome system and α-synuclein,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 9, pp. 3413–3418, 2005. View at Publisher · View at Google Scholar · View at Scopus
  150. D. Alvarez-Fischer, C. Henze, C. Strenzke et al., “Characterization of the striatal 6-OHDA model of Parkinson's disease in wild type and α-synuclein-deleted mice,” Experimental Neurology, vol. 210, no. 1, pp. 182–193, 2008. View at Publisher · View at Google Scholar · View at Scopus
  151. S. Rathke-Hartlieb, P. J. Kahle, M. Neumann et al., “Sensitivity to MPTP is not increased in Parkinson' s disease-associated mutant α-synuclein transgenic mice,” Journal of Neurochemistry, vol. 77, no. 4, pp. 1181–1184, 2001. View at Publisher · View at Google Scholar · View at Scopus
  152. M. Nieto, F. J. Gil-Bea, E. Dalfó et al., “Increased sensitivity to MPTP in human α-synuclein A30P transgenic mice,” Neurobiology of Aging, vol. 27, no. 6, pp. 848–856, 2006. View at Publisher · View at Google Scholar · View at Scopus
  153. Z. Dong, B. Ferger, J. Feldon, and H. Büeler, “Overexpression of Parkinson's disease-associated α-synucleinA53T by recombinant adeno-associated virus in mice does not increase the vulnerability of dopaminergic neurons to MPTP,” Journal of Neurobiology, vol. 53, no. 1, pp. 1–10, 2002. View at Publisher · View at Google Scholar · View at Scopus
  154. W. H. Yu, Y. Matsuoka, I. Sziráki et al., “Increased dopaminergic neuron sensitivity to 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) in transgenic mice expressing mutant A53T α-synuclein,” Neurochemical Research, vol. 33, no. 5, pp. 902–911, 2008. View at Publisher · View at Google Scholar · View at Scopus
  155. J. Peng, M. L. Oo, and J. K. Andersen, “Synergistic effects of environmental risk factors and gene mutations in Parkinson's disease accelerate age-related neurodegeneration,” Journal of Neurochemistry, vol. 115, no. 6, pp. 1363–1373, 2010. View at Publisher · View at Google Scholar · View at Scopus
  156. H. M. Gao, F. Zhang, H. Zhou, W. Kam, B. Wilson, and J. S. Hong, “Neuroinflammation and α-synuclein dysfunction potentiate each other, driving chronic progression of neurodegeneration in a mouse model of Parkinson's disease,” Environmental Health Perspectives, vol. 119, no. 6, pp. 807–814, 2011. View at Publisher · View at Google Scholar · View at Scopus
  157. P. O. Fernagut, C. B. Hutson, S. M. Fleming et al., “Behavioral and histopathological consequences of paraquat intoxication in mice: effects of α-synuclein over-expression,” Synapse, vol. 61, no. 12, pp. 991–1001, 2007. View at Publisher · View at Google Scholar · View at Scopus
  158. E. K. Richfield, M. J. Thiruchelvam, D. A. Cory-Slechta et al., “Behavioral and neurochemical effects of wild-type and mutated human α-synuclein in transgenic mice,” Experimental Neurology, vol. 175, no. 1, pp. 35–48, 2002. View at Publisher · View at Google Scholar · View at Scopus
  159. M. J. Thiruchelvam, J. M. Powers, D. A. Cory-Slechta, and E. K. Richfield, “Risk factors for dopaminergic neuron loss in human α-synuclein transgenic mice,” European Journal of Neuroscience, vol. 19, no. 4, pp. 845–854, 2004. View at Publisher · View at Google Scholar · View at Scopus
  160. N. M. Filipov, A. B. Norwood, and S. C. Sistrunk, “Strain-specific sensitivity to MPTP of C57BL/6 and BALB/c mice is age dependent,” NeuroReport, vol. 20, no. 7, pp. 713–717, 2009. View at Publisher · View at Google Scholar · View at Scopus
  161. S. Grealish, B. Mattsson, P. Draxler, and A. Björklund, “Characterisation of behavioural and neurodegenerative changes induced by intranigral 6-hydroxydopamine lesions in a mouse model of Parkinson's disease,” European Journal of Neuroscience, vol. 31, no. 12, pp. 2266–2278, 2010. View at Publisher · View at Google Scholar · View at Scopus
  162. R. Iancu, P. Mohapel, P. Brundin, and G. Paul, “Behavioral characterization of a unilateral 6-OHDA-lesion model of Parkinson's disease in mice,” Behavioural Brain Research, vol. 162, no. 1, pp. 1–10, 2005. View at Publisher · View at Google Scholar · View at Scopus
  163. R. K. Schwarting, M. Sedelis, K. Hofele et al., “Strain-dependent recovery of open-field behavior and striatal dopamine deficiency in the mouse MPTP model of Parkinson's disease,” Neurotoxicity Research, vol. 1, no. 1, pp. 41–56, 1999. View at Google Scholar
  164. M. Sedelis, K. Hofele, G. W. Auburger, S. Morgan, J. P. Huston, and R. K. W. Schwarting, “MPTP susceptibility in the mouse: behavioral, neurochemical, and histological analysis of gender and strain differences,” Behavior Genetics, vol. 30, no. 3, pp. 171–182, 2000. View at Publisher · View at Google Scholar · View at Scopus
  165. M. Lee, D. H. Hyun, B. Halliwell, and P. Jenner, “Effect of the overexpression of wild-type or mutant α-synuclein on cell susceptibility to insult,” Journal of Neurochemistry, vol. 76, no. 4, pp. 998–1009, 2001. View at Publisher · View at Google Scholar · View at Scopus
  166. M. Orth, S. J. Tabrizi, C. Tomlinson et al., “G209A mutant alpha synuclein expression specifically enhances dopamine induced oxidative damage,” Neurochemistry International, vol. 45, no. 5, pp. 669–676, 2004. View at Publisher · View at Google Scholar · View at Scopus
  167. T. H. Hamza, H. Chen, E. M. Hill-Burns et al., “Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson's disease modifier gene via interaction with coffee,” PLoS Genetics, vol. 7, no. 8, Article ID e1002237, 2011. View at Google Scholar
  168. P. Lewitt, “Recent advances in CSF biomarkers for Parkinson's disease,” Parkinsonism & Related Disorders, vol. 18, supplement 1, pp. S49–S51, 2012. View at Google Scholar
  169. K. D. van Dijk, C. E. Teunissen, B. Drukarch et al., “Diagnostic cerebrospinal fluid biomarkers for Parkinson's disease: a pathogenetically based approach,” Neurobiology of Disease, vol. 39, no. 3, pp. 229–241, 2010. View at Publisher · View at Google Scholar · View at Scopus
  170. M. Gerlach, W. Maetzler, K. Broich et al., “Biomarker candidates of neurodegeneration in Parkinson's disease for the evaluation of disease-modifying therapeutics,” Journal of Neural Transmission, vol. 119, no. 1, pp. 39–52, 2011. View at Publisher · View at Google Scholar · View at Scopus
  171. T. Alberio and M. Fasano, “Proteomics in Parkinson's disease: an unbiased approach towards peripheral biomarkers and new therapies,” Journal of Biotechnology, vol. 156, no. 4, pp. 325–337, 2011. View at Google Scholar
  172. R. C. Helmich, H. Mark, G. Deuschl et al., “Cerebral causes and consequences of parkinsonian resting tremor: a tale of two circuits?” Brain. In press.
  173. S. M. Van Rooden, F. Colas, P. Martínez-Martín et al., “Clinical subtypes of Parkinson's disease,” Movement Disorders, vol. 26, no. 1, pp. 51–58, 2011. View at Publisher · View at Google Scholar · View at Scopus