Advertisement

Journal of Neural Transmission

, Volume 115, Issue 10, pp 1413–1430 | Cite as

Neuroproteomics as a promising tool in Parkinson’s disease research

  • Ilse S. Pienaar
  • William M. U. Daniels
  • Jürgen Götz
Parkinson's Disease and Allied Conditions - Review Article

Abstract

Despite the vast number of studies on Parkinson’s disease (PD), its effective diagnosis and treatment remains unsatisfactory. Hence, the relentless search for an optimal cure continues. The emergence of neuroproteomics, with its sophisticated techniques and non-biased ability to quantify proteins, provides a methodology with which to study the changes in neurons that are associated with neurodegeneration. Neuroproteomics is an emerging tool to establish disease-associated protein profiles, while also generating a greater understanding as to how these proteins interact and undergo post-translational modifications. Furthermore, due to the advances made in bioinformatics, insight is created concerning their functional characteristics. In this review, we first summarize the most prominent proteomics techniques and then discuss the major advances in the fast-growing field of neuroproteomics in PD. Ultimately, it is hoped that the application of this technology will lead towards a presymptomatic diagnosis of PD, and the identification of risk factors and new therapeutic targets at which pharmacological intervention can be aimed.

Keywords

Alzheimer’s disease Biomarker Cerebrospinal fluid Mass spectrometry Neurodegenerative disease Neuroproteomics Parkinson’s disease 

Abbreviations

SNCA

Alpha-synuclein

AD

Alzheimer’s disease

SDS

Dodecyl sulphate

DA

Dopamine

ESI

Electrospray ionization

L-DOPA

Levodopa

LB

Lewy bodies

MS

Mass spectrometry

MPTP

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

6-OHDA

Parkinson’s disease

PD

6-Hydroxydopamine

SNpc

Substantia Nigra pars compacta

Notes

Acknowledgments

IP is supported by an International Brian Research Organization (IBRO) Fellowship and wishes to thank IBRO for the generous financial support of her work. This work was also supported by an NIH Fogarty International Centre Research Grant (R21DA018087 to Michael Zigmond) and the Medical Research Council (MRC) of South Africa. The financial assistance of the National Research Foundation (NRF) of South Africa towards this work is also acknowledged. JG is a Medical Foundation Fellow. JG is supported by the University of Sydney, the National Health & Medical Research Council (NHMRC), the Australian Research Council (ARC), the New South Wales Government through the Ministry for Science and Medical Research (BioFirst Program), the Nerve Research Foundation, the Medical Foundation (University of Sydney) and the Judith Jane Mason & Harold Stannett Williams Memorial Foundation.

References

  1. Abdi F, Quinn JF, Jankovic J, McIntosh M, Leverenz JB, Peskind E, Nixon R, Nutt J, Chung K, Zabetian C, Samii A, Lin M, Hattan S, Pan C, Wang Y, Jin J, Zhu D, Li GJ, Liu Y, Waichunas D, Montine TJ, Zhang J (2006) Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders. J Alzheimers Dis 9:293–348PubMedGoogle Scholar
  2. Aebersold R, Rist B, Gygi SP (2000) Quantitative proteome analysis: methods and applications. Ann NY Acad Sci 919:33–47PubMedGoogle Scholar
  3. Aksenov MY, Aksenova MV, Butterfield DA, Geddes JW, Markesbery WR (2001) Protein oxidation in the brain in Alzheimer’s disease. Neuroscience 103:373–383PubMedGoogle Scholar
  4. Alam Z, Daniel S, Lees A, Marsden D, Jenner P, Halliwell P (1997) A generalized increase in protein carbonyls in the brain in Parkinson’s but not incidental Lewy body disease. J Neurochem 69:1326–1329PubMedGoogle Scholar
  5. Andersen JK (2004) Oxidative stress in neurodegeneration: cause or consequence? Nat Med 10:S18–S25PubMedGoogle Scholar
  6. Arnaudeau S, Frieden M, Nakamura K, Castelbou C, Michalak M, Demaurex N (2002) Calreticulin differentially modulates calcium uptake and release in the endoplasmic reticulum and mitochondria. J Biol Chem 277:46696–46705PubMedGoogle Scholar
  7. Ascherio A, Zhang SM, Hernan MA, Kawachi I, Colditz GA, Speizer FE, Willett WC (2001) Prospective study of caffeine consumption and risk of Parkinson’s disease in men and women. Ann Neurol 50:56–63PubMedGoogle Scholar
  8. Ascherio A, Chen H, Weisskopf MG, O’Reilly E, McCullough ML, Calle EE, Schwarzschild MA, Thun MJ (2006) Pesticide exposure and risk for Parkinson’s disease. Ann Neurol 60:187–203Google Scholar
  9. Bandopadhyay R, Kingsbury AE, Cookson MR, Reid AR, Evans IM, Hope AD, Pittman AM, Lashley T, Canet-Aviles R, Miller DW, McLendon C, Strand C, Leonard AJ, Abou-Sleiman PM, Healy DG, Ariga H, Wood NW, de Silva R, Revesz T, Hardy JA, Lees AJ (2004) The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson’s disease. Brain 127:420–430PubMedGoogle Scholar
  10. Basso M, Giraudo S, Corpillo D, Bergamasco B, Lopiano L, Fasano M (2004) Proteome analysis of human substantia nigra in Parkinson’s disease. Proteomics 4:3943–3952PubMedGoogle Scholar
  11. Beal MF (2003) Mitochondria, oxidative damage, and inflammation in Parkinson’s disease. Ann NY Acad Sci 991:120–131PubMedGoogle Scholar
  12. Beal MF (2004) Mitochondrial dysfunction and oxidative damage in Alzheimer’s and Parkinson’s diseases and coenzyme Q10 as a potential treatment. J Bioenerg Biomembr 36:381–386PubMedGoogle Scholar
  13. Benecke R, Strümper P, Weiss H (1993) Electron transfer complexes I and IV of platelets are abnormal in Parkinson’s disease but normal in Parkinson-plus syndromes. Brain 116:1451–1463PubMedGoogle Scholar
  14. Bendiske J, Caba E, Brown QB, Bahr BA (2002) Intracellular deposition, microtubule destabilization, and transport failure: an “early” pathogenic cascade leading to synaptic decline. J Neuropathol Exp Neurol 61:640–650PubMedGoogle Scholar
  15. Benedetti MD, Bower JH, Maraganore DM, McDonnell SK, Peterson BJ, Ahlskog JE, Schaid DJ, Rocca WA (2000) Smoking, alcohol, and coffee consumption preceding Parkinson’s disease. Neurology 55:1350–1358PubMedGoogle Scholar
  16. Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F (1973) Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci 20:415–455PubMedGoogle Scholar
  17. Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT (2000) Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 3:1301–1306PubMedGoogle Scholar
  18. Bindoff LA, Birch-Machin M, Cartilidge NE, Parker WD, Turnbull DM (1991) Respiratory chain abnormalities in skeletal muscle from patients with Parkinson’s disease. J Neurol Sci 104:203–208PubMedGoogle Scholar
  19. Birkmayer W, Hornykiewicz O (1961) The effect of L-3,4-dihydroxyphenylalanine (L-DOPA) on akinesia in Parkinsonism. Wiener Klin. Wochenschr (1998) 73:787–788. Parkinsonism Relat Disord 4:59–60 (English translation)Google Scholar
  20. Blennow K, Wallin A, Agren H, Spenger C, Siegfried J, Vanmechelen E (1995) Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease? Mol Chem Neuropathol 26:231–245PubMedGoogle Scholar
  21. Bloch F, Houetto JL, Tezenas du Montcel S, Bonneville F, Etchepare F, Welter ML, Rivaud-Pechoux S, Hahn-Barma V, Maisonobe T, Behar C, Lazennec JY, Kurys E, Arnulf I, Bonnet AM, Agid Y (2006) Parkinson’s disease with camptocormia. J Neurol Neurosurg Psychiatry 77:1223–1228PubMedGoogle Scholar
  22. Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, Dekker MC, Squitieri F, Ibanez P, Joosse M, van Dongen JW, Vanacore N, van Swieten JC, Brice A, Meco G, van Duijn CM, Oostra BA, Heutink P (2003) Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299:256–259PubMedGoogle Scholar
  23. Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211PubMedGoogle Scholar
  24. Butterfield DA, Castegna A (2003) Proteomic analysis of oxidatively modified proteins in Alzheimer’s disease brain: insights into neurodegeneration. Amino Acids 25:419–425PubMedGoogle Scholar
  25. Butterfield DA, Gnjec A, Poon HF, Castegna A, Pierce WM, Klein JB, Martins RN (2006) Redox proteomics identification of oxidatively modified brain proteins in inherited Alzheimer’s disease: an initial assessment. J Alzheimers Dis 10:391–397PubMedGoogle Scholar
  26. Castegna A, Aksenov M, Thongboonkerd V, Klein JB, Pierce WM, Booze R, Markesbery WR, Butterfield DA (2002) Proteomic identification of oxidatively modified proteins in Alzheimer’s disease brain. Part II: Dihydropyrimidinase-related protein 2, alpha-enolase and heat shock cognate 71. J Neurochem 82:1524–1532PubMedGoogle Scholar
  27. Chen F, David D, Ferrari A, Götz J (2004) Posttranslational modifications of tau: role in human tauopathies and modeling in transgenic animals. Curr Drug Targets 5:503–515PubMedGoogle Scholar
  28. Chen L, Feany MB (2005) Alpha-synuclein phospohorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson’s disease. Nat Neurosci 8:657–663PubMedGoogle Scholar
  29. Chen H, Zhang SM, Schwarzschild MA, Hernan MA, Ascherio A (2005a) Physical activity and the risk of Parkinson disease. Neurology 64:664–669PubMedGoogle Scholar
  30. Chen Y, Wang Y, Yu H, Wang F, Xu W (2005b) The cross talk between protein kinase A- and RhoA-mediated signaling in cancer cells. Exp Biol Med 230:731–741Google Scholar
  31. Choi J, Levey AI, Weintraub ST, Rees HD, Gearing M, Chin LS, Li L (2004) Oxidative modifications and down-regulation of ubiquitin carboxyl-terminal hydrolase L1 associated with idiopathic Parkinson’s and Alzheimer’s diseases. J Biol Chem 279:13256–13264PubMedGoogle Scholar
  32. Choi J, Rees HD, Weintraub ST, Levey AI, Chin LS, Li L (2005) Oxidative modifications and aggregation of Cu, Zn-superoxide dismutase associated with Alzheimer and Parkinson diseases. J Biol Chem 280:11648–11655PubMedGoogle Scholar
  33. Clark I, Dodson M, Jiang C, Cao J, Huh J, Seol J, Yoo S, Hay B, Guo M (2006) Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441:1162–1166PubMedGoogle Scholar
  34. Conway KA, Lee SJ, Rochet JC, Ding TT, Williamson RE, Lansbury PT (2000) Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson’s disease: implications for pathogenesis and therapy. Proc Natl Acad Sci USA 97:571–576PubMedGoogle Scholar
  35. Conway KA, Rochet JC, Bieganski RM, Lansbury PT (2001) Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct. Science 294:1346–1349PubMedGoogle Scholar
  36. Cookson MR (2005) The biochemistry of Parkinson’s disease. Annu Rev Biochem 74:29–52PubMedGoogle Scholar
  37. Corthals GL, Wasinger VC, Hochstrasser DF, Wasinger VC, Hochstrasser DF, Sanchez JC (2000) The dynamic range of protein expression: a challenge for proteomic research. Electrophoresis 21:1104–1115PubMedGoogle Scholar
  38. Dai J, Buijs RM, Kamphorst W, Swaab DF (2002) Impaired axonal transport of cortical neurons in Alzheimer’s disease is associated with neuropathological changes. Brain Res 948:138–144PubMedGoogle Scholar
  39. Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39:889–909PubMedGoogle Scholar
  40. David DC, Hauptmann S, Scherping I, Schuessels K, Keil U, Rizzu P, Ravid R, Dröse S, Brandt U, Muller WE, Eckert A, Götz J (2005a) Proteomic and functional analysis reveal a mitochondrial dysfunction in P301L Tau transgenic mice. J Biol Chem 280:23802–23814PubMedGoogle Scholar
  41. David DC, Hoerndli F, Götz J (2005b) Functional genomics meets neurodegenerative disorders. Part 1: Transcriptomic and proteomic technology. Progress Neurobiol 76:153–168Google Scholar
  42. David DC, Ittner LM, Gehrig P, Nergenau D, Shepherd C, Halliday G, Gotz J (2006) ß-Amyloid treatment of two complementary P301L tau-expressing Alzheimer’s disease models reveals similar deregulated cellular processes. Proteomics 6:6566–6577PubMedGoogle Scholar
  43. Davidsson P, Sjögren M (2005) The use of proteomics in biomarker discovery in neurodegenerative diseases. Disease Markers 18:1–12Google Scholar
  44. Dawson TM, Dawson VL (2003) Molecular pathways of neurodegeneration in Parkinson’s disease. Science 302:819–822PubMedGoogle Scholar
  45. De Hoog CL, Mann M (2004) Proteomics. Annu Rev Genomics Hum Genet 5:267–293PubMedGoogle Scholar
  46. De Iuliis A, Grigoletto J, Recchia A, Giusti P, Arslan P (2005) A proteomic approach in the study of an animal model of Parkinson’s disease. Clin Chim Acta 357:202–209PubMedGoogle Scholar
  47. Deumens R, Blokland A, Prickaerts J (2002) Parkinson’s disease in rats: an evaluation of 6-OHDA lesions of the nigrostriatal pathway. Exp Neurol 175:303–317PubMedGoogle Scholar
  48. Dexter D, Wells F, Agid F, Agid Y, Lees AJ, Jenner P, Marsden CD (1987) Increased nigral iron content in postmortem parkisonian brain. Lancet 8569:1219–1220Google Scholar
  49. Dexter D, Sian J, Rose S, Hindmarsh JG, Mann VM, Cooper JM, Wells FR, Daniel SE, Lees AJ, Schapira AH et al (1994) Indices of oxidative stress and mitochondrial function in individuals with incidental Lewy body disease. Ann Neurol 35:38–44PubMedGoogle Scholar
  50. Di Monte DA, McCormack A, Petzinger G, Janson AM, Quik M, Langston WJ (2000) Relationship among nigrostriatal denervation, parkinsonism, and dyskinesias in the MPTP primate model. Mov Disord 15:459–466PubMedGoogle Scholar
  51. Escher N, Kaatz M, Melle M, Hipler C, Ziemer M, Driesch D, Wollina U, von Eggeling F (2007) Posttranslational modifications of transthyretin are serum markers in patients with mycosis fungiodes. Neoplasia 9:254–259PubMedGoogle Scholar
  52. Feany MB, Bender WW (2000) A Drosophila model of Parkinson’s disease. Nature 404:394–398PubMedGoogle Scholar
  53. Fialka I, Pasquali C, Lottspeich F, Ahorn H, Huber LA (1997) Subcellular fractionation of polarized epithelial cells and identification of organelle-specific proteins by two-dimensional gel electrophoresis. Electrophoresis 18:2582–2590PubMedGoogle Scholar
  54. Finehout EJ, Franck Z, Lee KH (2005) Complement protein isoforms in CSF as possible biomarkers for neurodegenerative disease. Dis Markers 21:93–101PubMedGoogle Scholar
  55. Fiskum G, Starkov A, Polster BM, Chinopoulos C (2003) Mitochondrial mechanisms of neural cell death and neuroprotective interventions in Parkinson’s disease. Ann NY Acad Sci 99:111–119Google Scholar
  56. Flament-Durand J, Couck AM (1979) Spongiform alterations in brain biopsies of presenile dementia. Acta Neuropathol (Berl) 46:159–162Google Scholar
  57. Fonteh AN, Harrington RJ, Huhmer AF, Biringer RG, Riggings JN, Harrington MG (2006) Identification of disease markers in human cerebrospinal fluid using lipidomic and proteomic methods. Dis Markers 22:39–64PubMedGoogle Scholar
  58. Fornai F, Schluter OM, Lenzi P, Ruffoli R, Ferrucci M, Lazzeri G, Busceti CL, Pontarelli F, Battaglia G, Pellegrini A, Nicoletti F, Ruggieri S, Paparelli A, Südhof TC (2005) Parkinson-like syndrome induced by continuous MPTP infusion: Convergent roles of the ubiquitin-proteasome system and alpha-synuclein. Proc Natl Acad Sci USA 102:3413–3418PubMedGoogle Scholar
  59. Forno LS, Langston JW, DeLanney LE, Irwin I, Ricaurte GA (1986) Locus coeruleus lesions and eosinophilic inclusions in MPTP-treated monkeys. Ann Neurol 20:449–455PubMedGoogle Scholar
  60. Fountoulakis M (2001) Proteomics: current technologies and applications in neurological disorders and toxicology. Amino Acids 21:363–381PubMedGoogle Scholar
  61. Fountoulakis M (2004) Application of proteomics technologies in the investigation of the brain. Mass Spectrom Rev 23:231–258PubMedGoogle Scholar
  62. Fountoulakis M, Kossida S (2006) Proteomics-driven progress in neurodegeneration research. Electrophoresis 27:1556–1573PubMedGoogle Scholar
  63. Fujiwara H, Hasegawa M, Dohmae N, Kawashima A, Masliah E, Goldberg MS, Shen J, Takio K, Iwatsubo T (2002) Alpha-synuclein is phosphorylated in synucleinopathy lesions. Nat Cell Biol 4:160–164PubMedGoogle Scholar
  64. Gasser T (2005) Genetics of Parkinson’s disease. Curr Opin Neurol 18:363–369PubMedGoogle Scholar
  65. Giasson BI, Duda JE, Murray IV, Chen Q, Souza JM, Hurtig HI, Ischiropoulos H, Trojanowski JQ, Lee VM (2000) Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science 294:1346–1349Google Scholar
  66. Giasson BI, Van Deerlin VM (2008) Mutations in LRRK2 as a cause of Parkinson’s disease. Neurosignals 16:99–105PubMedGoogle Scholar
  67. Goedert M (2001) Alpha-synuclein and neurodegenerative diseases. Nat Rev Neurosci 2:492–501PubMedGoogle Scholar
  68. Goldknopf IL, Sheta EA, Bryson J, Folsom B, Wilson C, Duty J, Yen AA, Appel SH (2006) Complement C3c and related protein biomarkers in amyotrophic lateral sclerosis and Parkinson’s disease. Biochem Biophys Res Commun 342:1034–1039PubMedGoogle Scholar
  69. Goldman JE, Yen SH, Chiu FC, Peress NS (1983) Lewy bodies of Parkinson’s disease contain neurofilament antigens. Science 221:1082–1084PubMedGoogle Scholar
  70. Gorell JM, Johnson CC, Rybicki BA, Peterson EL, Richardson RJ (1998) The risk of Parkinson’s disease with exposure to pesticides, farming, well water, and rural living. Neurology 50:1346–1350PubMedGoogle Scholar
  71. Görg A, Postel W, Günther S, Weser J (1985) Improved horizontal two-dimensional electrophoresis with hybrid isoelectric focusing in immobilized pH gradients in the first dimension and laying-on transfer to the second dimension. Electrophoresis 12:653–658Google Scholar
  72. Götz J, Tolnay M, Barmettler R, Ferrari A, Bürki K, Goedert M, Probst A, Nitsch RM (2001) Human tau transgenic mice. Towards an animal model for neuro- and glialfibrillary lesion formation. Adv Exp Med Biol 487:71–83PubMedGoogle Scholar
  73. Götz J, Streffer JR, David D, Schild A, Hoerndli F, Pennanen L, Kurosinski P, Chen F (2004) Transgenic animal models of Alzheimer’s disease and related disorders: Histopathology, behavior and therapy. Mol Psychiatry 9:664–683PubMedGoogle Scholar
  74. Götz J, Ittner LM, Kins S (2006) Do axonal defects in tau and amyloid precursor protein transgenic animals model axonopathy in Alzheimer’s disease? J Neurochem 98:993–1006PubMedGoogle Scholar
  75. Götz J, Deters N, Doldissen A, Bokhari L, Ke Y, Wiesner A, Schonrock N, Ittner LM (2007) A decade of tau transgenic animal models and beyond. Brain Pathol 17:91–103PubMedGoogle Scholar
  76. Götz J, David D, Hoerndli F, Ke YD, Schonrock N, Wiesner A, Fath T, Bokhari L, Lim YA, Deters N, Ittner LM (2008) Functional genomics dissects pathomechanisms in tauopathies: mitosis failure and unfolded protein response. Neurodegener Dis 5:179–181PubMedGoogle Scholar
  77. Graves PR, Haystead TA (2002) Molecular biologist’s guide to proteomics. Microbiol Mol Biol Rev 66:39–63PubMedGoogle Scholar
  78. Greene JC, Whitworth AJ, Kuo I, Andrews LA, Feany MB, Pallanck LJ (2003) Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc Natl Acad Sci USA 100:4078–4083PubMedGoogle Scholar
  79. Gu M, Cooper JM, Taanman JW, Schapira AHV (1998) Mitochondrial DNA transmission of the mitochondrial defect in Parkinson’s disease. Ann Neurol 44:177–186PubMedGoogle Scholar
  80. Gygi SP, Rist B, Gerber SA, Turecek F, Gelb MH, Aebersold R (1999) Quantitative analysis of complex protein mixtures using isotope coded affinity tags. Nat Biotechnol 17:994–999PubMedGoogle Scholar
  81. Haas RH, Nasirian F, Nakano K, Ward D, Pay M, Hill R, Shults CW (1995) Low platelet mitochondrial complex I and complex II/III activity in early untreated Parkinson’s disease. Ann Neurol 37:714–722PubMedGoogle Scholar
  82. Hanash S (2004) HUPO initiatives relevant to clinical proteomics. Mol Cell Proteomics 3:298–301PubMedGoogle Scholar
  83. Hardy J, Cookson MR, Singleton A (2003) Genes and parkinsonism. Lancet Neurol 2:221–228PubMedGoogle Scholar
  84. Hardy J, Cai H, Cookson MR, Gwinn-Hardy K, Singleton A (2006) Genetics of Parkinson’s disease and parkinsonism. Ann Neurol 60:389–398PubMedGoogle Scholar
  85. Hansen L, Cai H, Cookson MR, Gwinn-Hardy K, Singleton A (1990) The Lewy body variant of Alzheimer’s disease: a clinical and pathologic entity. Neurology 40:1–8PubMedGoogle Scholar
  86. He Y, Le WD, Appel SH (2002) Role of fcgamma receptors in nigral cell injury induced by Parkinson’s disease immunoglobulin injection into mouse substantia niga. Exp Neurol 176:322–327PubMedGoogle Scholar
  87. Heimlick G, Cidlowski JA (2006) Selective role of intracellular chloride in the regulation of the intrinsic but not extrinsic pathway of apoptosis in Jurkat T-cells. J Biol Chem 281:2232–2241Google Scholar
  88. Hernan MA, Takkouche B, Caamano-Isorna F, Gestal-Otero JJ (2002) A meta-analysis of coffee drinking, cigarette smoking, and the risk of Parkinson’s disease. Ann Neurol 52:276–284PubMedGoogle Scholar
  89. Hoving S, Gerrits B, Voshol H, Müller D, Roberts RC, van Oostrum J (2002) Preparative two-dimensional gel electrophoresis at alkaline pH using narrow range immobilized pH gradients. Proteomics 2:127–134PubMedGoogle Scholar
  90. Hutchens TW, Yip TT (1993) New desorption strategies for the mass spectrometric analysis of macromolecules. Rapid Commun Mass Spectrom 7:576–580Google Scholar
  91. Hoerndli F, David DC, Götz J (2005) Functional Genomics meets neurodegenerative disorders. Part II: application and data integration. Prog Neurobiol 76:169–188PubMedGoogle Scholar
  92. Hoglinger GU, Carrard G, Michel PO, Medja F, Lombes A, Ruberg M, Friguet B, Hirsch EC (2003) Dysfunction of mitochondrial complex I and the proteasome: interactions between two biochemical deficits in a cellular model of Parkinson’s disease. J Neurochem 86:1297–1307PubMedCrossRefGoogle Scholar
  93. Horvatovich P, Govorukhina NI, Reijmers TH, van der Zee AG, Suits F, Bischoff R (2007) Chip-LC-MS for label-free profiling of human serum. Electrophoresis 28:4493–4505PubMedGoogle Scholar
  94. Hourcade DE, Mitchell L, Kuttner-Kondo LA, Atkinson JP, Medof ME (2002) Decay-accelerating factor (DAF), complement receptor 1 (CR1), and factor H dissociate the complement AP C3 convertase (C3bBb) via sites on the type A domain of Bb. J Biol Chem 277:1107–1112PubMedGoogle Scholar
  95. Huber LA, Pfaller K, Vietor K (2003) Organelle proteomics: implications for subcellular fractionation in proteomics. Circ Res 92:962–968PubMedGoogle Scholar
  96. Hühmer AF, Biringer RG, Amato H, Fonteh AN, Harrington MG (2006) Protein analysis in human cerebrospinal fluid: physiological aspects, current progress and future challenges. Disease Markers 22:2–26Google Scholar
  97. Ichikawa H, Sugimoto T (2005) Peptide 19 in the rat vagal and glossopharyngeal sensory ganglia. Brain Res 1038:107–112PubMedGoogle Scholar
  98. Jain KK (2004) Role of pharmacoproteomics in the development of personalized medicine. Pharmacogenomics 5:331–336PubMedGoogle Scholar
  99. Jensen PH, Hager H, Nielsen MS, Højrup P, Gliemaann J, Jakes R (1999) α-Synuclein binds to tau and stimulates the protein kinase A-catalyzed tau phosphorylation of serine residues 262 and 356. J Biol Chem 274:25481–25489PubMedGoogle Scholar
  100. Jin J, Meredith GE, Chen L, Zhou Y, Xu J, Shie FS, Lockhart P, Zhang J (2005) Quantitative proteomic analysis of mitochondrial proteins: relevance to Lewy body formation and Parkinson’s disease. Mol Brain Res 134:119–138PubMedGoogle Scholar
  101. Jin J, Li GJ, Davis J, Zhu D, Wang Y, Pan C, Zhang J (2007) Identification of novel proteins associated with both alpha-synuclein and DJ–1. Mol Cell Proteomics 6:845–859PubMedGoogle Scholar
  102. Johanson RA, Sarau HM, Foley JJ, Slemmon JR (2000) Calmodulin Binding Peptide PEP–19 Modulates Activation of Calmodulin Kinase II in situ. J Neurosci 20:2860–2866PubMedGoogle Scholar
  103. Johnson MD, Yu LR, Conrads TP, Kinoshita Y, Uo T, McBee JK, Veenstra TD, Morrison RS (2005) The proteomics of neurodegeneration. Am J Pharmacogenomics 5:259–270PubMedGoogle Scholar
  104. Jorge I, Casas EM, Villar M, Ortega-Pérez I, López-Ferrer D, Martínez-Ruiz A, Carrera M, Marina A, Martínez P, Serrano H, Cañas B, Were F, Gallardo JM, Lamas S, Redondo JM, García-Dorado D, Vázquez J (2007) High-sensitivity analysis of specific peptides in complex samples by selected MS/MS ion monitoring and linear ion trap mass spectrometry: Application to biological studies. J Mass Spectrom 42:1391–1403PubMedGoogle Scholar
  105. Kaur D, Yantiri F, Rajagopalan S, Kumar J, Mo JQ, Boonplueang R, Viswanath V, Jacobs R, Yang L, Beal MF, DiMonte D, Volitaskis I, Ellerby L, Cherny RA, Bush AI, Andersen JK (2003) Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: A novel therapy for Parkinson’s disease. Neuron 37:899–909PubMedGoogle Scholar
  106. Kinumi T, Kimata J, Taira T, Ariga H, Niki E (2004) Cysteine-106 of DJ-1 is the most sensitive cysteine residue to hydrogen peroxide-mediated oxidation in vivo in human. Biochem Biophys Res Commun 317:722–728PubMedGoogle Scholar
  107. Kirik D, Rosenblad C, Burger C, Lundberg C, Johansen TE, Muzyczka N, Mandel RJ, Bjorklund A (2002) Parkinson-like neurodegeneration induced by targeted overexpression of alpha-synuclein in the nigrostriatal system. J Neurosci 22:2780–2791PubMedGoogle Scholar
  108. Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392:605–608PubMedGoogle Scholar
  109. Klein C, Lohmann-Hedrich K (2007) Impact of recent genetic findings in Parkinson’s disease. Curr Opin Neurol 20:453–464PubMedGoogle Scholar
  110. Klose J (1975) Protein mapping by combined isoelectric focusing and electrophoresis of mouse tissues. A novel approach to testing for induced point mutations in mammals. Humangenetik 26:231–243PubMedGoogle Scholar
  111. Klucken J, Shin Y, Hyman BT, McLean PJ (2004) A single amino acid substitution differentiates Hsp70-dependent effects on alpha-synuclein degradation and toxicity. Biochem Biophys Res Commun 325:367–373PubMedGoogle Scholar
  112. Kurosinski P, Guggisberg M, Götz J (2002) Alzheimer’s and Parkinson’s disease - overlapping or synergistic pathologies? Trends Mol Med 8:3–5PubMedGoogle Scholar
  113. Krüger R, Kuhn W, Müller T, Woitalla D, Graeber M, Kösel S, Przuntek H, Epplen JT, Schöls L, Riess O (1998) Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson’s disease. Nat Genet 18:106–108PubMedGoogle Scholar
  114. Lee MY, Park SE, Chung KC, Oh YJ (2003) Proteomic analysis reveals upregulation of calreticulin in murine dopaminergic neuronal cells after treatment with 6-hydroxidopamine. Neurosci Lett 352:17–20PubMedGoogle Scholar
  115. Lee WD, Appel SH (2004) Mutant genes responsible for Parkinson’s disease. Curr Opin Pharmacol 4:79–84Google Scholar
  116. Lee SJ (2008) Origins and effects of extracellular alpha-synuclein: Implications in Parkinson’s disease. J Mol Neurosci 34:17–22PubMedGoogle Scholar
  117. Leroy E, Boyer R, Auburger G, Leube B, Ulm G, Mezey E, Harta G, Brownstein MJ, Jonnalagada S, Chernova T, Dehejia A, Lavedan C, Gasser T, Steinbach PJ, Wilkinson KD, Polymeropoulos MH (1998) The ubiquitin pathway in Parkinson’s disease. Nature 395:451–452PubMedGoogle Scholar
  118. Limousin P, Krack P, Pollak P, Benazzouz A, Ardouin C, Hoffmann D, Benabid AL (1998) Electrical stimulation of the subthalamic nucleus in advanced Parkinson’s disease. N Engl J Med 339:1105–1111PubMedGoogle Scholar
  119. Link AJ, Eng J, Schieltz DM, Carmack E, Mize GJ, Morris DR, Garvik BM, Yates JRIII (1999) Direct analysis of protein complexes using mass spectrometry. Nat Biotechnol 17:676–682PubMedGoogle Scholar
  120. Lippa CF, Fujiwara H, Mann DM, Giasson B, Baba M, Schmidt ML, Nee LE, O’Connell B, Pollen DA, St George-Hyslop P, Ghetti B, Nochlin D, Bird TD, Cairns NJ, Lee VM, Iwatsubo T, Trojanowski JQ (1998) Lewy bodies contain altered alpha-synuclein in brains of many familial Alzheimer’s disease patients with mutations in presenilin and amyloid precursor protein genes. Am J Pathol 153:1365–1370PubMedGoogle Scholar
  121. Lipton MS, Pasa-Tolic L, Anderson GA (2002) Global analysis of the deinococcus radiodurans proteome by using accurate mass tags. Proc Natl Acad Sci USA 99:11049–11054PubMedGoogle Scholar
  122. Liu H, Miller E, van de Water B, Stevens JL (2001) Endoplasmic reticulum stress proteins block oxidant-5nd 4ced Ca2+ increase and cell death. J Biol Chem 273:12858–12862Google Scholar
  123. Liu H, Zang Y, Wang J, Wang D, Zhou C, Cai Y, Qian X (2006) Method for quantitative proteomics research by using metal element chelated tags coupled with mass spectrometry. Anal Chem 78:6614–6621PubMedGoogle Scholar
  124. Lopes MF, Melov S (2002) Applied proteomics: Mitochondrial proteins and effect on function. Circ Res 90:380–389Google Scholar
  125. Manetto V, Perry G, Tabaton M, Mulvihill P, Fried VA, Smith HT, Gambetti P, Autilio-Gambetti L (1988) Ubiquitin is associated with abnormal cytoplasmic filaments characteristic of neurodegenerative diseases. Proc Natl Acad Sci USA 85:4501–4505PubMedGoogle Scholar
  126. Manning-Boğ AB, McCormack AL, Li J, Uversky VN, Fink AL, Di Monte DA (2002) The herbicide paraquat causes up-regulation and aggregation of alpha-synuclein in mice: paraquat and alpha-synuclein. J Biol Chem 277:1641–1644PubMedGoogle Scholar
  127. Matsuoka Y, Vila M, Lincoln S, McCormack A, Picciano M, LaFrancois J, Yu X, Dickson D, Langston WJ, McGowan E, Farrer M, Hardy J, Duff K, Przedborski S, Di Monte DA (2001) Lack of nigral pathology in transgenic mice expressing human alpha-synuclein driven by the tyrosine hydroxylase promoter. Neurobiol Dis 8:535–539PubMedGoogle Scholar
  128. Mercken M, Fischer I, Kosik KS, Nixon RA (1995) Three distinct axonal transport rates for tau, tubulin and other microtubule-associated proteins: evidence for dynamic interactions of tau with microtubules in vivo. J Neurosci 15:8259–8267PubMedGoogle Scholar
  129. Meyer HE, Stuhler K (2007) High-performance proteomics as a tool in biomarker discovery. Proteomics 7:18–26PubMedGoogle Scholar
  130. Michell AW, Lewis SJG, Foltynie T, Barker RA (2004) Biomarkers and Parkinson’s disease. Brain 127:1693–1705PubMedGoogle Scholar
  131. Miksys S, Tyndale RF (2006) Nicotine induces brain CYP enzymes: Relevance to Parkinson’s disease. J Neural Transm Suppl 70:177–180PubMedCrossRefGoogle Scholar
  132. Miller N, Noble E, Jones D, Burn D (2006) Hard to swallow: dysphagia in Parkinson’s disease. Age Ageing 35:614–618PubMedGoogle Scholar
  133. Mitsumoto A, Nakagawa Y (2001) DJ-1 is an indicator for endogenous reactive oxygen species elicited by endotoxin. Free Radic Res 35:885–893PubMedGoogle Scholar
  134. Mitsumoto A, Nakagawa Y, Takeuchi A, Okawa K, Iwamatsu A, Takanezawa Y (2001) Oxidized forms of peroxiredoxins and DJ-1 on two-dimensional gels increased in response to sublethal levels of paraquat. Free Radic Res 35:301–310PubMedGoogle Scholar
  135. Montgomery EB Jr, Koller WC, LaMantia TJ, Newman MC, Swanson-Hyland AW, Kaszniak AW, Lyons K (2000a) Early detection of probable idiopathic Parkinson’s disease I. Development of a diagnostic test battery. Mov Disord 15:467–473PubMedGoogle Scholar
  136. Montgomery EB Jr, Lyons K, Koller WC (2000b) Early detection of probable idiopathic Parkinson’s disease II. A prospective application of a diagnostic test battery. Mov Disord 15:474–478PubMedGoogle Scholar
  137. Moseley MA (2001) Current trends in differential expression proteomics: Isotopically coded tags. Trends Biotechnol 19:S10–S16PubMedGoogle Scholar
  138. Mueller LN, Rinner O, Schmidt A, Letarte S, Bodenmiller B, Brusniak MY, Vitek O, Aebersold R, Müller M (2007) SuperHirn—a novel tool for high resolution LC-MS-based peptide/protein profiling. Proteomics 7:3470–3480PubMedGoogle Scholar
  139. Murakami T, Shoji M, Imai Y, Inoue H, Kawarabayashi T, Matsubara E, Harigaya Y, Sasaki A, Takahashi R, Abe K (2004) Pael-R is accumulated in Lewy bodies of Parkinson’s disease. Ann Neurol 55:439–442PubMedGoogle Scholar
  140. Nakamura K, Bossy-Wetzel E, Burns K, Fadel MP, Lozyk M, Goping IS, Opas M, Bleackley RC, Green DR, Michalak M (2000) Changes in endoplasmic reticulum luminal environment affect cell sensitivity to apoptosis. J Cell Biol 150:731–740PubMedGoogle Scholar
  141. Neumann M, Muller V, Gorner K, Kretzschmar HA, Haas C, Kahle PJ (2004) Pathological properties of the Parkinson’s disease associated protein DJ-1 in alpha-synucleinopathies and tauopathies: relevance for multiple system atrophy and Pick’s disease. Acta Neuropathol (Berl) 107:489–496Google Scholar
  142. Nissbaum RL, Ellis C (2003) Alzheimer’s disease and Parkinson’s disease. N Engl J Med 348:1356–1364Google Scholar
  143. Nunez MT, Osorio A, Tapia V, Vergara A, Mura CV (2001) Iron-induced oxidative stress up-regulates calreticulin levels in intestinal epithelial (Caco-2) cells. J Cell Biochem 82:660–665PubMedGoogle Scholar
  144. O’Farrell PH (1975) High resolution two-dimensional electrophoresis of proteins. J Biol Chem 250:4007–4021PubMedGoogle Scholar
  145. Olanow CW, Tatton WG (1999) Etiology and pathogenesis of Parkinson’s disease. Annu Rev Neurosci 22:123–144PubMedGoogle Scholar
  146. Olsen JV, Andersen JR, Nielsen PA, Nielsen ML, Figeys D, Mann M, Wisniewski JR (2004) HysTag–a novel proteomic quantification tool applied to differential display analysis of membrane proteins from distinct areas of mouse brain. Mol Cell Proteomics 3:82–92PubMedGoogle Scholar
  147. Onn SE, Mann M (2005) Mass spectrometry-based proteomics turn quantitative. Nat Chem Biol 1:252–262Google Scholar
  148. Opiteck GJ, Lewis KC, Jorgenson JW, Anderegg RJ (1997) Comprehensive on-line LC/LC/MS of proteins. Anal Chem 69:1518–1524PubMedGoogle Scholar
  149. Paciello O, Wojcik S, Engel WK, McFerrin J, Askanas V (2006) Parkin and its association with alpha-synuclein and AbetaPP in inclusion-body myositis and AbetaPP—overexpressing cultured human muscle fibers. Acta Myol 25:13–22PubMedGoogle Scholar
  150. Palacino JJ, Sagi D, Goldberg MS, Krauss S, Motz C, Wacker M, Klose J, Shen J (2004) Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J Biol Chem 279:18614–18622PubMedGoogle Scholar
  151. Pan S, Rush J, Peskind ER, Galasko D, Chung K, Quinn J, Jankovic J, Leverenz JB, Zabetian C, Pan C, Wang Y, Oh JH, Gao J, Zhang J, Montine T, Zhang J (2008) Application of targeted quantitative proteomics analysis in human cerebrospinal fluid using a liquid chromatography matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometer (LC MALDI TOF/TOF) platform. J Proteome Res 7:720–730PubMedGoogle Scholar
  152. Pandey A, Mann M (2000) Proteomics to study genes and genomes. Nature 405:837–846PubMedGoogle Scholar
  153. Pannese E, Procacci P, Ledda M (1996) Ultrastructural localization of actin in then cell biology of rat spinal ganglion neurons. Anat Embryol 194:527–531PubMedGoogle Scholar
  154. Park J, Lee SB, Lee S, Kim Y, Song S, Kim S, Bae E, Kim J, Shong M, Kim JM, Chung J (2006) Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature 441:1157–1161PubMedGoogle Scholar
  155. Parker WD, Boyson SJ, Parks JK (1989) Abnormalities of the electron transport chain in idiopathic Parkinson’s disease. Ann Neurol 26:719–723PubMedGoogle Scholar
  156. Parker WD, Parks JK, Swerdlow RH (2008) Complex I deficiency in Parkinson’s disease frontal cortex. Brain Res 1189:215–218PubMedGoogle Scholar
  157. Pasquali C, Fialka I, Huber LA (1997) Preparative two-dimensional gel electrophoresis of membrane proteins. Electrophoresis 18:2573–2581PubMedGoogle Scholar
  158. Paweletz CP, Trock B, Pennanen M, Tsangaris T, Magnant C, Liotta LA, Petricoin EFIII (2001) Proteomic patterns of nipple aspirate fluids obtained by SELDI-TOF: potential for new biomarkers to aid in the diagnosis of breast cancer. Dis Markers 17:301–307PubMedGoogle Scholar
  159. Periquet M, Corti O, Jacquier S, Brice A (2005) Proteomic analysis of parkin knockout mice: alterations in energy metabolism, protein handling and synaptic function. J Neurochem 95:1259–1276PubMedGoogle Scholar
  160. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 276:2045–2047PubMedGoogle Scholar
  161. Praprotnik D, Smith MA, Richey PL, Vinters HV, Perry G (1996) Filament heterogeneity within the dystrophic neurites of senile plaques suggests blockage of fast axonal transport in Alzheimer’s disease. Acta Neuropathol 91:226–235PubMedGoogle Scholar
  162. Racette BA, Tabbal SD, Jennings D, Good L, Perlmutter JS, Evanoff B (2005) Prevalence of parkinsonism and relationship to exposure in a large sample of Alabama welders. Neurology 64:230–235PubMedGoogle Scholar
  163. Rego AC, Oliveira CR (2003) Mitochondrial dysfunction and reactive oxygen species in excitotoxicity and apoptosis: implications for the pathogenesis of neurodegenerative diseases. Neurochem Res 28:1563–1574PubMedGoogle Scholar
  164. Reinders J, Lewandrowski U, Moebius J, Wagner Y, Sickmann A (2004) Challenges in mass spectrometry-based proteomics. Proteomics 4:3686–3703PubMedGoogle Scholar
  165. Richard S, Brion J-P, Couck AM, Flament-Durand J (1989) Accumulation of smooth endoplasmic reticulum in Alzheimer’s disease: new morphological evidence of axoplasmic flow disturbances. J Submicrosc Cytol Pathol 21:461–467PubMedGoogle Scholar
  166. Riederer P, Wuketich S (1976) Time course of nigrostriatal degeneration in parkinson’s disease: a detailed study of influential factors in human brain amine analysis. J Neural Transm 38:277–301PubMedGoogle Scholar
  167. Righetti PG, Campostrini N, Pascali J, Hamdan M, Astner H (2004) Quantitative proteomics: a review of different methodologies. Eur J Mass Spectrom 10:335–348Google Scholar
  168. Romeo M, Espina V, Lowenthal M, Espina BH, Petricoin EF, Liotta LA (2005) CSF proteome: a protein repository for potential biomarker identification. Expert Rev Proteomics 2:57–70PubMedGoogle Scholar
  169. Ross GW, Abbott RD, Petrovitch H, Morens DM, Grandinetti A, Tung KH, Tanner CM, Masaki KH, Blanchette PL, Curb JD, Popper JS, White LR (2000) Association of coffee and caffeine intake with risk of Parkinson’s disease. JAMA 283:2674–2679PubMedGoogle Scholar
  170. Schapira AHV, Cooper JM, Dexter D, Jenner P, Clark JB, Marsden CD (1989) Mitochondrial complex I deficiency in Parkinson’s disease. Lancet 1:1269PubMedGoogle Scholar
  171. Schapira AH, Cooper JM, Dexter D, Clark JB, Jenner P, Marsden CD (1990) Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem 54:823–827PubMedGoogle Scholar
  172. Schapira AH (1998) Mitochondrial dysfunction in neurodegenerative disorders. Biochem Biophys Acta 1366:225–233PubMedGoogle Scholar
  173. Schapira AH (2004) Disease modification in Parkinson’s disease. Lancet Neurol 3:362–368PubMedGoogle Scholar
  174. Schmidt A, Kellermann J, Lottspeich F (2005) A novel strategy for quantitative proteomics using isotope-coded protein labels. Proteomics 5:4–15PubMedGoogle Scholar
  175. Schulenborg T, Schmidt O, van Hall A, Meyer HE, Hamacher M, Marcus K (2006) Proteomics in neurodegeneration—disease driven approaches. J Neural Transm 113:1055–1073PubMedGoogle Scholar
  176. Seniuk NA, Tatton WG, Greenwood CE (1990) Dose-dependent destruction of the coeruleus-cortical and nigral-striatal projections by MPTP. Brain Res 527:7–20PubMedGoogle Scholar
  177. Setsuie R, Wada K (2007) The functions of UCH-L1 and its relation to neurodegenerative diseases. Neurochem Internat 51:105–111Google Scholar
  178. Shahani N, Brandt R (2002) Functions and malfunctions of the tau-proteins. Cell Mol Life Sci 59:1668–1680PubMedGoogle Scholar
  179. Shen J, Cookson M (2004) Mitochondria and dopamine: new insights into recessive parkinsonism. Neuron 43:301–304PubMedGoogle Scholar
  180. Shendelman S, Jonason A, Martinat C, Leete T, Abeliovich A (2004) DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formation. PLoS Biol 2:e362PubMedGoogle Scholar
  181. Sheta EA, Appel SH, Goldknopf IL (2006) 2-D gel blood serum biomarkers reveal differential clinical proteomics of the neurodegenerative diseases. Expert Rev Proteomics 3:45–62PubMedGoogle Scholar
  182. Shoffner JM, Watts RL, Juncos JL, Torroni A, Wallace DC (1991) Mitochondrial oxidative phosporylation defects in Parkinson’s disease. Ann Neurol 30:332–339PubMedGoogle Scholar
  183. Simpson RJ (2003) Purifying proteins for proteomics: a laboratory manual. Cold Spring Harbor Laboratory Press, New YorkGoogle Scholar
  184. Sjögren M, Davidsson P, Tullberg L, Minthon L, Wallin A, Wikkelso C, Granérus AK, Vanderstichele H, Vanmechelen E, Blennow K (2001) Both total and phosphorylated tau are increased in Alzheimer’s disease. J Neurol Neurosurg Psych 70:624–630Google Scholar
  185. Skold K, Svensson M, Nilsson A, Zhang X, Nydahl K, Caprioli RM, Svenningsson P, Andren PE (2006) Decreased striatal levels of PEP-19 following MPTP lesion in the mouse. J Proteome Res 5:262–269PubMedGoogle Scholar
  186. Spillantini MG, Schmidt ML, Lee VM-Y, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388:839–840PubMedGoogle Scholar
  187. Spiro RG, Zhu Q, Bhoyroo V, Soling HD (1996) Definition of the lectin-like properties of the molecular chaperone, calreticulin, and demonstration of its copurification with endomannosidase from rat liver Golgi. J Biol Chem 271:11588–11594PubMedGoogle Scholar
  188. Stühler K, Joppich C, Stephan C, Jung K, Müller M, Schmidt O, van Hall A, Hamacher M, Urfen W, Meyer HE, Marcus K (2006) Pilot study of the Human Proteome Organisation Brain Proteome Project: applying different 2-DE techniques to monitor proteomic changes during murine brain development. Proteomics 6:4899–4913PubMedGoogle Scholar
  189. Sultana R, Boyd-Kimball D, Cai J, Pierce WM, Klein JB, Merchant M, Butterfield DA (2007) Proteomics analysis of the Alzheimer’s disease hippocampal proteome. J Alzheimers Dis 11:153–164PubMedGoogle Scholar
  190. Svensson M, Skold K, Nilsson A, Falth M, Svenningsson P, Andren PE (2007) Neuropeptidomics: expanding proteomics downwards. Biochem Soc Trans 35:588–593PubMedGoogle Scholar
  191. Swerdlow RH, Parks JK, Miller SW, Tuttle JB, Trimmer PA, Sheehan JP, Bennett JP Jr (1996) Origin and functional consequences of the complex I defect in Parkinson’s disease. Ann Neurol 40:663–671PubMedGoogle Scholar
  192. Taira T, Saito Y, Niki T, Iguchi-Ariga SM, Takahashi K, Ariga H (2004) EMBO Rep 5:213–218PubMedGoogle Scholar
  193. The deep-brain stimulation for Parkinson study group (2001) Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson’s disease. N Eng J Med 345:956–963Google Scholar
  194. Tinazzi M, Del Vesco C, Fincati E, Ottaviani S, Smania N, Moretto G, Fiaschi A, Martino D, Defazio G (2006) Pain and motor complications in Parkinson’s disease. J Neurol Neurosurg Psych 77:822–825Google Scholar
  195. Tribl F, Marcus K, Bringmann G, Meyer HE, Gerlach M, Riederer P (2006a) Proteomics of the human brain: sub-proteomes might hold the key to handle brain complexity. J Neural Transm 113:1041–1054PubMedGoogle Scholar
  196. Tribl F, Marcus K, Meyer HE, Bringmann G, Gerlach M, Riederer P (2006b) Subcellular proteomics reveals neuromelanin granules to be a lysosome-related organelle. J Neural Transm 113:741–749PubMedGoogle Scholar
  197. Trojanowski JQ, Lee VM (1998) Aggregation of neurofilament and alpha-synuclein proteins in Lewy bodies: implications for the pathogenesis of Parkinson disease and Lewy body dementia. Arch Neurol 55:151–152PubMedGoogle Scholar
  198. Truong DD, Bhidayasiri R, Wolters E (2007) Management of non-motor symptoms in advanced Parkinson disease. J Neurol Sci 266:216–228PubMedGoogle Scholar
  199. Tseng H-M, Su PC, Liu H-M, Liou H-H, Yen R-F (2007) Bilateral subthalamotomy for advanced Parkinson disease. Surg Neurol 68:S43–S50PubMedGoogle Scholar
  200. Utal AK, Stopka AL, Roy M, Coleman PD (1998) PEP-19 immunohistochemistry defines the basal ganglia and associated structures in the adult human brain and is dramatically reduced in Huntington’s disease. Neuroscience 86:1055–1063PubMedGoogle Scholar
  201. Utton MA, Connell J, Asuni AA, Van Slegtenhorst M, Hutton M, De Silva R, Lees AJ, Miller CC, Anderton BH (2002) The slow axonal transport of the microtubule-associated protein tau and the transport rates of different isoforms and mutants in cultured neurons. J Neurosci 22:6394–6400PubMedGoogle Scholar
  202. Vercauteren FGG, Bergeron JJM, Vandesande F, Arckens L, Quirion R (2004) Proteomic approaches in brain research and neuropharmacology. Eur J Pharmacol 500:385–398PubMedGoogle Scholar
  203. Vila-Carriles WH, Zhou ZH, Bubien JK, Fuller CM, Benos DJ (2007) Participation of the chaperone Hsc70 in the trafficking and functional expression of ASIC2 in glioma cells. J Biol Chem 282:34381–34391PubMedGoogle Scholar
  204. von Bohlen und Halbach O, Schober A, Krieglstein K (2004) Genes, proteins, and neurotoxins involved in Parkinson’s disease. Prog Neurobiol 73:151–177Google Scholar
  205. Waragai M, Nakai M, Wei J, Fujita M, Mizuno H, Ho G, Masliah E, Akatsu H, Yokochi F, Hashimoto M (2007) Plasma levels of DJ-1 as a possible marker for progression of sporadic Parkinson’s disease. Neurosci Lett 425:18–22PubMedGoogle Scholar
  206. Washburn MP, Yates JR (2000) Analysis of the microbial proteome. Curr Opin Microbiol 3:292–297PubMedGoogle Scholar
  207. Washburn MP, Ulaszek R, Deciu C, Schieltz DM, Yates JR (2002) Analysis of quantitative proteomic data generated via multidimensional protein identification technology. Anal Chem 74:1650–1657PubMedGoogle Scholar
  208. Wiederkehr F (1991) Analysis of cerebrospinal fluid proteins by electrophoresis. J Chromatogr 569:281–296PubMedGoogle Scholar
  209. Wilkins MR, Sanchez JC, Gooley AA, Appel RD, Humphery-Smith I, Ochstrasser DF, Williams KL (1996) Progress with proteome projects: why all proteins expressed by a genome should be identified and how to do it. Biotechnol Genet Eng Rev 13:19–50PubMedGoogle Scholar
  210. Wilkinson KD, Lee KM, Deshpande S, Duerksen-Hughes P, Boss JM, Pohl J (1989) The neuron-specific protein PGP9.5 is a ubiquitin carboxyl-terminal hydrolase. Science 246:670–673PubMedGoogle Scholar
  211. Wolters EC, Francot C, Bergmans P, Winogrodzka A, Booij J, Berendse HW, Stoof HC (2000) Preclinical (premotor) Parkinson’s disease. J Neurol 247:II103–II109PubMedGoogle Scholar
  212. Wolters DA, Washburn MP, Yates JR (2001) An automated multidimensional protein identification technology for shotgun proteomics. Anal Chem 73:5683–5690PubMedGoogle Scholar
  213. Wood-Allum CA, Barber SC, Kirby J, Heath P, Holden H, Mead R, Higginbottom A, Allen S, Beaujeux T, Alexson SE, Ince PG, Shaw PJ (2006) Impairment of mitochondrial anti-oxidant defence in SOD1-related motor neuron injury and amelioration by ebselen. Brain 128:1686–1706Google Scholar
  214. Wu CC, MacCoss MJ (2002) Shotgun proteomics: tools for the analysis of complex biological systems. Curr Opin Mol Ther 4:242–250PubMedGoogle Scholar
  215. Wu TL (2006) Two-dimensional difference gel electrophoresis. Methods Mol Biol 328:71–95PubMedGoogle Scholar
  216. Xun Z, Sowell RA, Kaufman TC, Clemmer DE (2007) Lifetime proteomic profiling of an A30P α-synuclein drosophila model of Parkinson’s disease. J Proteome Res 6:3729–3738PubMedGoogle Scholar
  217. Yao H, Sem DS (2005) Cofactor fingerprinting with STD NMR to characterize proteins of unknown function: identification of a rare cCMP cofactor preference. FEBS Lett 579:661–666PubMedGoogle Scholar
  218. Yokota T, Sugawara K, Ito K, Takahashi R, Ariga H, Mizusawa H (2003) Down regulation of DJ-1 enhances cell death by oxidative stress, ER stress, and proteasome inhibition. Biochem Biophys Res Commun 312:1342–1348PubMedGoogle Scholar
  219. Yoritaka A, Hattori N, Uchida K, Tanaka M, Stadtman E, Mizuno Y (1996) Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson’s disease. Proc Natl Acad Sci USA 93:2696–2701PubMedGoogle Scholar
  220. Zang L, Toy DP, Hancock WS, Sgroi DC, Karger BL (2004) J Prot Res 3:604–612Google Scholar
  221. Zetterberg H, Ruetschi U, Portelius E, Brinkmalm G, Andreasson U, Blennow K, Brinkmalm A (2008) Clinical proteomics in neurodegenerative disorders. Acta Neurol Scand (in press)Google Scholar
  222. Zigmond MJ, Burke RE (2002) Pathophysiology of Parkinson’s disease. In: Davis KL, Coyle J, Charney D, Nemeroff C (eds) Fifth Generation of Progress. Lippincott Williams & Wilkins, Philadelphia, pp 1781–1794Google Scholar
  223. Zhang B, Higuchi M, Yoshiyama Y, Ishihara T, Forman MS, Martinez D, Joyce S, Trojanowski JQ, Lee VM (2004) Retarded axonal transport of R406 W mutant tau in transgenic mice with a neurodegenerative tauopathy. J Neurosci 24:4657–4667PubMedGoogle Scholar
  224. Zhou Y, Gu G, Goodlett DR, Zhang T, Pan C, Montine TJ, Montine KS, Aebersold RH, Zhang J (2004) Analysis of α-synuclein associated proteins by quantitative proteomics. J Biol Chem 279:39155–39164PubMedGoogle Scholar
  225. Zhou W, Freed CR (2005) DJ-1 up-regulates glutathione synthesis during oxidative stress and inhibits A53T α-synuclein toxicity. J Biol Chem 280:43150–43158PubMedGoogle Scholar
  226. Zhou W, Zhu M, Wilson MA, Petsko GA, Fink LA (2006) The oxidation state of DJ-1 regulates its chaperone activity toward alpha-synuclein. J Mol Biol 356:1036–1048PubMedGoogle Scholar
  227. Zhu M, Qin ZJ, Hu D, Munishkina LA, Fink AL (2006) Alpha-synuclein can function as an antioxidant preventing oxidation of unsaturated lipid in vesicles. Biochemistry 45:8135–8142PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Ilse S. Pienaar
    • 1
    • 2
  • William M. U. Daniels
    • 3
  • Jürgen Götz
    • 4
  1. 1.Department of Medical PhysiologyUniversity of StellenboschMatielandSouth Africa
  2. 2.Department of Physiology, Anatomy and GeneticsUniversity of OxfordOxfordUK
  3. 3.School of MedicineUniversity of Kwazulu-NatalDurbanSouth Africa
  4. 4.Alzheimer’s and Parkinson’s Disease Laboratory, Brain and Mind Research InstituteUniversity of SydneySydneyAustralia

Personalised recommendations