Neurotoxicity Research

, Volume 11, Issue 3–4, pp 219–240 | Cite as

Model fusion: The next phase in developing animal models for parkinson’s disease

Article

Abstract

Within the past 25 years, discoveries of environmental and monogenetic forms of parkinsonism have shaped the direction of Parkinson’s disease (PD) research and development of experimental systems to study PD. In this review, we outline a remarkable array ofin vivo models available, with particular emphasis on their benefits and pitfalls and the contribution each has made to enhance our understanding of pathological mechanisms involved in PD. Further, we discuss the increasingly popular approach of “model fusion” to create a new generation of animal systems in which to study gene-environment interactions, and the usefulness of such models in capturing the most common events underlying PD.

Keywords

Parkinson’s disease Animal modeling MPTP Transgenic animals Genes Environment 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alam M and WJ Schmidt (2002) Rotenone destroys dopa- minergic neurons and induces parkinsonian symptoms in rats.Behav. Brain Res. 136(1), 317–324.PubMedCrossRefGoogle Scholar
  2. Bandopadhyay R, AE Kingsbury, MR Cookson, AR Reid, IM Evans, AD Hope, AM Pittman, T Lashley, R Canet-Aviles, DW Miller, C McLendon, C Strand, AJ Leonard, PM Abou-Sleiman, DG Healy, H Ariga, NW Wood, R de Silva, T Revesz, JA Hardy and AJ Lees (2004) The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson’s disease.Brain 127(Pt. 2), 420–430.PubMedCrossRefGoogle Scholar
  3. Betarbet R, RM Canet-Aviles, TB Sherer, PG Mastroberardino, C McLendon, JH Kim, S Lund, HM Na, G Taylor, NF Bence, R Kopito, BB Seo, T Yagi, A Yagi, G Klinefelter, MR Cookson and JT Greenamyre (2006) Intersecting pathways to neurodegeneration in Parkinson’s disease, effects of the pesticide rotenone on DJ-1, alpha-synuclein, and the ubiquitin-proteasome system.Neurobiol. Dis. 22(2), 404–420.PubMedCrossRefGoogle Scholar
  4. Betarbet R, TB Sherer, G MacKenzie, M Garcia-Osuna, AV Panov and JT Greenamyre (2000) Chronic systemic pesticide exposure reproduces features of Parkinson’s disease.Nat. Neurosci. 3(12), 1301–1306.PubMedCrossRefGoogle Scholar
  5. Bonifati V, P Rizzu, MJ van Baren, O Schaap, GJ Breedveld, E Krieger, MC Dekker, F Squitieri, P Ibanez, M Joosse, JW van Dongen, N Vanacore, JC van Swieten, A Brice, G Meco, CM van Duijn, BA Oostra and P Heutink (2003) Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism.Science 299(5604), 256–259.PubMedCrossRefGoogle Scholar
  6. Bonneh-Barkay D, SH Reaney, JW Langston and DA Di Monte (2005) Redox cycling of the herbicide paraquat in microglial cultures.Brain Res. Mol. Brain Res. 134(1), 52–56.PubMedCrossRefGoogle Scholar
  7. Brooks AI, CA Chadwick, HA Gelbard, DA Cory-Slechta and HJ Federoff (1999) Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss.Brain Res. 823(1–2), 1–10.PubMedCrossRefGoogle Scholar
  8. Burns RS, CC Chiueh, SP Markey, MH Ebert, DM Jacobowitz and IJ Kopin (1983) A primate model of parkinsonism, selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.Proc. Natl. Acad. Sci. USA 80, 4546–4550.PubMedCrossRefGoogle Scholar
  9. Canet-Aviles RM, MA Wilson, DW Miller, R Ahmad, C McLendon, S Bandyopadhyay, MJ Baptista, D Ringe, GA Petsko and MR Cookson (2004) The Parkinson’s disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization.Proc. Natl. Acad. Sci. USA 101(24), 9103–9108.PubMedCrossRefGoogle Scholar
  10. Casarejos MJ, J Menendez, RM Solano, JA Rodriguez-Navarro, J Garcia de Yebenes and MA Mena (2006) Susceptibility to rotenone is increased in neurons from parkin null mice and is reduced by minocycline.J. Neurochem. 97(4), 934–946.PubMedCrossRefGoogle Scholar
  11. Chan P, JW Langston, I Irwin, LE DeLanney and DA Di Monte (1993) 2-deoxyglucose enhances 1-methyl-4-pheny1-1, 2,3,6-tetrahydropyridine-induced ATP loss in the mouse brain.J. Neurochem. 61(2), 610–616.PubMedGoogle Scholar
  12. Chandra S, G Gallardo, R Fernandez-Chacon, OM Schluter and TC Sudhof (2005) Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration.Cell 123(3), 383–396.PubMedCrossRefGoogle Scholar
  13. Chartier-Harlin MC, J Kachergus, C Roumier, V Mouroux, X Douay, S Lincoln, C Levecque, L Larvor, J Andrieux, M Hullihan, N Waucquier, L Defebyre, P Amouyel, M Farrer and A Destee (2004) Alpha-synuclein locus duplication as a cause of familial Parkinson’s disease.Lancet 364(9440), 1167–1169.PubMedCrossRefGoogle Scholar
  14. Chen L, B Cagniard, T Matthews, S Jones, HC Koh, Y Ding, PM Carvey, Z Ling, UJ Kang and X Zhuang (2005) Age-dependent motor deficits and dopaminergic dysfunction in DJ-1 null mice.J. Biol. Chem. 280(22), 21418–21426.PubMedCrossRefGoogle Scholar
  15. Chung KK and TM Dawson (2004) Parkin and Hsp70 sacked by BAG5.Neuron 44(6), 899–901.PubMedCrossRefGoogle Scholar
  16. Chung KK, B Thomas, X Li, O Pletnikova, JC Troncoso, L Marsh, VL Dawson and TM Dawson (2004) S-nitrosylation of parkin regulates ubiquitination and compromises parkin’s protective function.Science 304(5675), 1328–13231.PubMedCrossRefGoogle Scholar
  17. Cleeter MW, JM Cooper and AH Schapira (1992) Irreversible inhibition of mitochondrial complex I by 1-methyl-4-phenylpyridinium, evidence for free radical involvement.J. Neurochem. 58(2), 786–789.PubMedCrossRefGoogle Scholar
  18. Dalfo E, T Gomez-Isla, JL Rosa, M Nieto Bodelon, M Cuadrado Tejedor, M Barrachina, S Ambrosio and I Ferrer (2004) Abnormal α-synuclein interactions with Rab proteins in α-synuclein A30P transgenic mice.J. Neuropathol. Exp. Neurol. 63(4), 302–313.PubMedGoogle Scholar
  19. Daniels AJ and JF Reinhard Jr (1988) Energy-driven uptake of the neurotoxin 1-methyl-4-phenylpyridinium into chromaffin granules via the catecholamine transporter.J. Biol. Chem. 263(11), 5034–5036.PubMedGoogle Scholar
  20. Dauer W, N Kholodilov, M Vila, AC Trillat, R Goodchild, KE Larsen, R Staal, K Tieu, Y Schmitz, CA Yuan, M Rocha, V Jackson-Lewis, S Hersch, D Sulzer, S Przedborski, R Burke and R Hen (2002) Resistance of alpha-synuclein null mice to the parkinsonian neurotoxin MPTP.Proc. Natl. Acad. Sci. USA 99(22), 14524–14529.PubMedCrossRefGoogle Scholar
  21. Drolet RE, B Behrouz, KJ Lookingland and JL Goudreau (2004) Mice lacking alpha-synuclein have an attenuated loss of striatal dopamine following prolonged chronic MPTP administration.Neurotoxicology 25(5), 761–769.PubMedCrossRefGoogle Scholar
  22. Duda JE, BI Giasson, ME Mabon, DC Miller, LI Golbe, VM Lee and JQ Trojanowski (2002) Concurrence of alpha-synuclein and tau brain pathology in the Contursi kindred.Acta Neuropathol. (Berl.) 104(1), 7–11.CrossRefGoogle Scholar
  23. Farrer M, P Chan, R Chen, L Tan, S Lincoln, D Hernandez, L Forno, K Gwinn-Hardy, L Petrucelli, J Hussey, A Singleton, C Tanner, J Hardy and JW Langston (2001) Lewy bodies and parkinsonism in families with parkin mutations.Ann. Neurol. 50(3), 293–300.PubMedCrossRefGoogle Scholar
  24. Farrer M, T Destee, E Becquet, F Wavrant-De Vrieze, V Mouroux, F Richard, L Defebvre, S Lincoln, J Hardy, P Amouyel and MC Chartier-Harlin (2000) Linkage exclusion in French families with probable Parkinson’ s disease.Mov. Disord. 15(6), 1075–1083.PubMedCrossRefGoogle Scholar
  25. Farrer M, J Kachergus, L Forno, S Lincoln, DS Wang, M Hulihan, D Maraganore, K Gwinn-Hardy, Z Wszolek, D Dickson and JW Langston (2004) Comparison of kindreds with parkinsonism and alpha-synuclein genomic multiplications.Ann. Neurol. 55(2), 174–179.PubMedCrossRefGoogle Scholar
  26. Ferrante RJ, JB Schulz, NW Kowall and MF Beal (1997) Systemic administration of rotenone produces selective damage in the striatum and globus pallidus, but not in the substantia nigra.Brain Res. 753(1), 157–162.PubMedCrossRefGoogle Scholar
  27. Fleming SM, J Salcedo, PO Fernagut, E Rockenstein, E Masliah, MS Levine and MF Chesselet (2004) Early and progressive sensorimotor anomalies in mice overex-pressing wild-type human α-synuclein.J. Neurosci. 24, 9434–9440.PubMedCrossRefGoogle Scholar
  28. Fornai F, P Lenzi, M Gesi, M Ferrucci, G Lazzeri, L Capobianco, A de Blasi, G Battaglia, F Nicoletti, S Ruggieri and A Paparelli (2004) Similarities between methamphetamine toxicity and proteasome inhibition.Ann. NY Acad. Sci. 1025, 162–170.PubMedCrossRefGoogle Scholar
  29. Fornai F, OM Schluter, P Lenzi, M Gesi, R Ruffoli, M Ferrucci, G Lazzeri, CL Busceti, F Pontarelli, G Battaglia, A Pellegrini, F Nicoletti, S Ruggieri, A Paparelli and TC Sudhof (2005) Parkinson-like syndrome induced by continuous MPTP infusion, convergent roles of the ubiq-uitin-proteasome system and alpha-synuclein.Proc. Natl. Acad. Sci. USA 102(9), 3413–8.PubMedCrossRefGoogle Scholar
  30. Forno LS, JW Langston, LE DeLanney, I Irwin and GA Ricaurte (1986) Locus ceruleus lesions and eosinophilic inclusions in MPTP-treated monkeys. Ann.Neurol. 20(4), 449–455.Google Scholar
  31. Fuchs J, C Nilsson, J Kachergus, M Munz, EM Larsson, B Schule, JW Langston, FA Middleton, OA Ross, M Hulihan, T Gasser and MJ Farrer (2007) Phenotypic variation in a large Swedish pedigree due to SNCA duplication and triplication.Neurology 2007 Jan. 24; [Epub ahead of print]Google Scholar
  32. Fung HC, G Xiromerisiou, JR Gibbs, YR Wu, J Eerola, V Gourbali, O Hellstrom, CM Chen, J Duckworth, A Papadimitriou, PJ Tienari, GM Hadjigeorgiou, J Hardy and AB Singleton (2006) Association of tau haplotype-tagging polymorphisms with Parkinson’s disease in diverse ethnic Parkinson’s disease cohorts.Neurodegen. Dis. 3(6), 327–333.CrossRefGoogle Scholar
  33. Gainetdinov RR, F Fumagalli, YM Wang, SR Jones, AI Levey, GW Miller and MG Caron (1998) Increased MPTP neurotoxicity in vesicular monoamine transporter 2 heterozygote knockout mice.J. Neurochem. 70(5), 1973–1978.PubMedGoogle Scholar
  34. Galvin JE, VM Lee and JQ Trojanowski (2001) Synuclein-opathies, clinical and pathological implications.Arch. Neurol. 58(2), 186–190.PubMedCrossRefGoogle Scholar
  35. German DC, KF Manaye, CL White 3rd, DJ Woodward, DD McIntire, WK Smith, RN Kalaria and DM Mann (1992) Disease-specific patterns of locus coeruleus cell loss.Ann. Neurol. 32(5), 667–676.PubMedCrossRefGoogle Scholar
  36. Giasson BI, JE Duda, SM Quinn, B Zhang, JQ Trojanowski and VM Lee (2002) Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein.Neuron 34(4), 521–533.PubMedCrossRefGoogle Scholar
  37. Gispert S, D Del Turco, L Garrett, A Chen, DJ Bernard, J Hamm-Clement, HW Korf, T Deller, H Braak, G Auburger and RL Nussbaum (2003) Transgenic mice expressing mutant A53T human alpha-synuclein show neuronal dysfunction in the absence of aggregate formation.Mol. Cell. Neurosci. 24(2), 419–429.PubMedCrossRefGoogle Scholar
  38. Goers J, AB Manning-Boğ, AI McCormack, IS Millett, S Donlach, DA Di Monte, VN Uversky and AL Fink (2003) Nuclear localization of alpha-synuclein and its interaction with histones.Biochemistry 42(28), 8465–8471.PubMedCrossRefGoogle Scholar
  39. Goldberg MS, SM Fleming, JJ Palacino, C Cepeda, HA Lam, A Bhatnagar, EG Meloni, N Wu, LC Ackerson, GJ Klapstein, M Gajendiran, BL Roth, MF Chesselet, NT Maidment, MS Levine and J Shen (2003) Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons.J. Biol. Chem. 278(44), 43628–43635.PubMedCrossRefGoogle Scholar
  40. Goldberg MS, A Pisani, M Haburcak, TA Vortherms, T Kitada, C Costa, Y Tong, G Martella, A Tscherter, A Martins, G Bernardi, BL Roth, EN Pothos, P Calabresi and J Shen (2005) Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1.Neuron 45(4), 489–496.PubMedCrossRefGoogle Scholar
  41. Gomez-Isla T, MC Irizarry, A Mariash, B Cheung, O Soto, S Schrump, J Sondel, L Kotilinek, J Day, MA Schwarzschild, JH Cha, K Newell, DW Miller, K Ueda, AB Young, BT Hyman and KH Ashe (2003) Motor dysfunction and gliosis with preserved dopaminergic markers in human alpha-synuclein A3 0P transgenic mice.Neurobiol. Aging 24, 245–258.PubMedCrossRefGoogle Scholar
  42. Guilarte TR (2001) Is methamphetamine abuse a risk factor in parkinsonism?Neurotoxicology 22(6), 725–731.PubMedCrossRefGoogle Scholar
  43. Hayashi S, K Wakabayashi, A Ishikawa, H Nagai, M Saito, M Maruyama, T Takahashi, T Ozawa, S Tsuji and H Takahashi (2000) An autopsy case of autosomal-recessive uvenile parkinsonism with a homozygous exon 4 deletion in the parkin gene.Mov. Disord. 15(5), 884–888.PubMedCrossRefGoogle Scholar
  44. Heikkila RE, A Hess and RC Duvoisin (1984) Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydro-pyridine in mice.Science 224(4656), 1451–1453.PubMedCrossRefGoogle Scholar
  45. Hoglinger GU, J Feger, A Prigent, PP Michel, K Parain, P Champy, M Ruberg, WH Oertel and EC Hirsch (2003) Chronic systemic complex I inhibition induces a hypokinetic multisystem degeneration in rats.J. Neurochem. 84(3), 491–502.PubMedCrossRefGoogle Scholar
  46. Hoglinger GU, A Lannuzel, ME Khondiker, PP Michel, C Duyckaerts, J Feger, P Champy, A Prigent, F Medja, A Lombes, WH Oertel, M Ruberg and EC Hirsch (2005) The mitochondrial complex I inhibitor rotenone triggers a cerebral tauopathy.J. Neurochem. 95(4), 930–939.PubMedCrossRefGoogle Scholar
  47. Itier JM, P Ibanez, MA Mena, N Abbas, C Cohen-Salmon, GA Bohme, M Laville, J Pratt, O Corti, L Pradier, G Ret, C Joubert, M Periquet, F Araujo, J Negroni, MJ Casarejos, S Canals, R Solano, A Serrano, E Gallego, M Sanchez, P Denefle, J Benavides, G Tremp, TA Rooney, A Brice and J Garcia de Yebenes (2003) Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse.Hum. Mol. Genet. 12(18), 2277–2291.PubMedCrossRefGoogle Scholar
  48. Javitch JA, RJ D’Amato, SM Strittmatter and SH Snyder (1985) Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6 -tetrahydropyridine, uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity.Proc. Natl. Acad. Sci. USA 82(7), 2173–7.PubMedCrossRefGoogle Scholar
  49. Kahle PJ, M Neumann, L Ozmen and C Haass (2000a) Physiology and pathophysiology of alpha-synuclein. Cell culture and transgenic animal models based on a Parkinson’s disease-associated protein.Ann. NY Acad. Sci. 920, 33–41.PubMedGoogle Scholar
  50. Kahle PJ, M Neumann, L Ozmen, V Muller, H Jacobsen, A Schindzielorz, M Okochi, U Leimer, H van Der Putten, A Probst, E Kremmer, HA Kretzschmar and C Haass (2000b) Subcellular localization of wild-type and Parkinson’s disease-associated mutant alpha-synuclein in human and transgenic mouse brain.J. Neurosci. 20(17), 6365–6373.PubMedGoogle Scholar
  51. Kaur D, F Yantiri, S Rajagopalan, J Kumar, JQ Mo, R Boonplueang. V Viswanath, R Jacobs, L Yang, MF Beal, D DiMonte, I Volitaskis, L Ellerby, RA Cherny, AI Bush and JK Andersen (2003) Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicityin vivo: a novel therapy for Parkinson’s disease.Neuron 37(6), 899–909.PubMedCrossRefGoogle Scholar
  52. Kholodilov NG, M Neystat, TF Oo, SE Lo, KE Larsen, D Sulzer and RE Burke (1999) Increased expression of rat synuclein in the substantia nigra pars compacta identified by mRNA differential display in a model of developmental target injury.J. Neurochem. 73(6), 2586–2599.PubMedCrossRefGoogle Scholar
  53. Kholodilov NG, TF Oo and RE Burke (1999) Synuclein expression is decreased in rat substantia nigra following induction of apoptosis by intrastriatal 6-hydroxydopamine.Neurosci. Lett. 275(2), 105–108.PubMedCrossRefGoogle Scholar
  54. Kim RH, M Peters, Y Jang, W Shi, M Pintillie, GC Fletcher, C DeLuca, J Liepa, L Zhou, B Snow, RC Binari, AS Manoukian, MR Bray, FF Liu, MS Tsao and TW Mak (2005) DJ-1, a novel regulator of the tumor suppressor PTEN.Cancer Cell 7(3), 263–273.PubMedCrossRefGoogle Scholar
  55. Kim RH, PD Smith, H Aleyasin, S Hayley, MP Mount, S Pownall, A Wakeham, AJ You-Ten, SK Kalia, P Horne, D Westaway, AM Lozano, H Anisman, DS Park and TW Mak (2005) Hypersensitivity of DJ-1-deficient mice to 1 -methyl-4-phenyl-1, 2,3,6-tetrahydropyrindine (MPTP) and oxidative stress.Proc. Natl. Acad. Sci. USA 102(14), 5215–5220.PubMedCrossRefGoogle Scholar
  56. Kitada T, S Asakawa, N Hattori, H Matsumine, Y Yamamura, S Minoshima, M Yokochi, Y Mizuno and N Shimizu (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism.Nature 392(6676), 605–608.PubMedCrossRefGoogle Scholar
  57. Klivenyi P, D Siwek, G Gardian, L Yang, A Taarkov, C Cleren, RJ Ferrante, NW Kowall, A Abellovich and MF Beal (2006) Mice lacking alpha-synuclein are resistant to mitochondrial toxins.Neurobiol Dis. 21(3), 541–548.PubMedCrossRefGoogle Scholar
  58. Kontopoulos E., JD Parvin and MB Feany (2006) α-Synuclein acts in the nucleus to inhibit histone acetylation and promote neurotoxicity.Hum. Mol. Genet. 15(20), 3012–3023.PubMedCrossRefGoogle Scholar
  59. Kostrzewa RM, JP Kostrzewa, R Brus, RA Kostrzewa and P Nowak (2006) Proposed animal model of severe Parkinson’s disease, neonatal 6-hydroxydopamine lesion of dopaminergic innervation of striatum.J. Neural Transm. Suppl.70, 277–279.CrossRefGoogle Scholar
  60. Kowall NW, P Hantraye, E Brouillet, MF Beal, AC McKee and RJ Ferrante (2000) MPTP induces alpha-synuclein aggregation in the substantia nigra of baboons.Neuroreport 11(1), 211–213.PubMedCrossRefGoogle Scholar
  61. Kruger R, W Kuhn, T Muller, D Woitalla, M Graeber, S Kosel, H Przuntek, JT Epplen, L Schols and O Riess (1998) Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson’s disease.Nat. Genet. 18(2), 106–108.PubMedCrossRefGoogle Scholar
  62. Lan J and DH Jiang (1997) Desferrioxamine and vitamin E protect against iron and MPTP-induced neurodegeneration in mice.J. Neural Transm. 104(4–5), 469–481.PubMedCrossRefGoogle Scholar
  63. Langston JW (2006) The Parkinson’s complex, parkinsonism is just the tip of the iceberg.Ann. Neurol. 59(4), 591–6.PubMedCrossRefGoogle Scholar
  64. Langston JW, P Ballard, JW Tetrud and I Irwin (1983) Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis.Science 219(4587), 979–980.PubMedCrossRefGoogle Scholar
  65. Langston JW, LS Forno, CS Rebert and I Irwin (1984) Selective nigral toxicity after systemic administration of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyrine (MPTP) in the squirrel monkey.Brain Res. 292(2), 390–394.PubMedCrossRefGoogle Scholar
  66. Lapointe N, M St-Hilaire, MG Martinoli, J Blanchet J Blanchet, P Gould, C Rouillard and F Cicchetti (2004) Rotenone induces non-specific central nervous system and systemic toxicity.FASEB J. 18(6), 717–719.PubMedGoogle Scholar
  67. Lee MK, W Stirling, Y Xu, X Xu, D Qui, AS Mandir, TM Dawson, NG Copeland, NA Jenkins and DL Price (2002) Human alpha-synuclein-harboring familial Parkinson’s disease-linked Ala-53 -> Thr mutation causes neuro-degenerative disease with alpha-synuclein aggregation in transgenic mice.Proc. Natl. Acad. Sci. USA 99(13), 8968–8973.PubMedCrossRefGoogle Scholar
  68. Ling ZD, Q Chang, JW Lipton, CW Tong, TM Landers and PM Carvey (2004) Combined toxicity of prenatal bacterial endotoxin exposure and postnatal 6-hydroxydopamine in the adult rat midbrain.Neuroscience 124(3), 619–628.PubMedCrossRefGoogle Scholar
  69. Ling Z, Y Zhu, C Tong, JA Snyder, JW Lipton and PM Carvey (2006) Progressive dopamine neuron loss following supra-nigral lipopolysaccharide (LPS) infusion into rats exposed to LPS prenatally.Exp Neurol. 199(2), 499–512.PubMedCrossRefGoogle Scholar
  70. Liou HH, MC Tsai, CJ Chen, JS Jeng, YC Chang, SY Chen and RC Chen (1997) Environmental risk factors and Parkinson’s disease, a case-control study in Taiwan.Neurology 48(6), 1583–1588.PubMedGoogle Scholar
  71. Lockhart PJ, CA O’Farrell and MJ Farrer (2004) It’s a double knock-out! The quaking mouse is a spontaneous deletion of parkin and parkin co-regulated gene (PACRG).Mov. Disord. 19(1), 101–104.PubMedCrossRefGoogle Scholar
  72. Manning-Boğ AB, AL McCormack, J Li, VN Uversky, AL Fink and DA Di Monte (2002) The herbicide paraquat causes up-regulation and aggregation of alpha-synuclein in mice, paraquat and α-synuclein.J. Biol. Chem. 277, 1641–1644.PubMedCrossRefGoogle Scholar
  73. Manning-Boğ AB, AL McCormack, MG Purisai, LM Bolin and DA Di Monte (2003) α-Synuclein over-expression protects against paraquat-induced neurodegeneration.J. Neurosci. 23(8), 3095–3099.PubMedGoogle Scholar
  74. Martin LJ, Y Pan, AC Price, W Sterling, NG Copeland, NA Jenkins, DL Price and MK Lee (2006) Parkinson’s disease α-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death.J. Neurosci. 26(1), 41–50.PubMedCrossRefGoogle Scholar
  75. Masliah E, E Rockenstein, I Veinbergs, M Mallory, M Hashimoto, A Takeda, Y Sagara, A Sisk and L Mucke (2000) Dopaminergic loss and inclusion body formation in alpha-synuclein mice, implications for neurodegenerative disorders.Science 287(5456), 1265–1269.PubMedCrossRefGoogle Scholar
  76. Matsuoka Y, M Vila, S Lincoln, A McCormack, M Picciano, J LaFrancois, X Yu, D Dickson, JW Langston, E McGowan, M Farrer, J Hardy, K Duff, S Przedborski and DA Di Monte (2001) Lack of nigral pathology in transgenic mice expressing human alpha-synuclein driven by the tyrosine hydroxylase promoter.Neurobiol. Dis. 8(3), 535–539.PubMedCrossRefGoogle Scholar
  77. Mauceli G, CI Busceti, A Pellegrini, P Soldani, P Lenzi, A Paparelli and F Fornai (2006) Over-expression of alpha-synuclein following methamphetamine, is it good or bad?Ann. NY Acad. Sci. 1074, 191–197.PubMedCrossRefGoogle Scholar
  78. McCormack AL and DA Di Monte (2003) Effects of L-dopa and other amino acids against paraquat-induced nigros-triatal degeneration.J. Neurochem. 85(1), 82–86.PubMedGoogle Scholar
  79. McCormack AL, M Thiruchelvam, AB Manning-Boğ, C Thiffault, JW Langston, DA Cory-Slechta and DA Di Monte (2002) Environmental risk factors and Parkinson’s disease, selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat.Neurobiol. Dis. 10(2), 119–127.PubMedCrossRefGoogle Scholar
  80. Miller GW, JD Erickson, JT Perez, SN Penland, DC Mash, DB Rye and AI Levey (1999) Immunochemical analysis of vesicular monoamine transporter (VMAT2) protein in Parkinson’s disease.Exp. Neurol. 156(1), 138–148.PubMedCrossRefGoogle Scholar
  81. Mochizuki H, H Imai, K Endo, K Yokomizo, Y Murata, N Hattori and Y Mizuno (1994) Iron accumulation in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahy-dropyridine (MPTP)-induced hemiparkinsonian monkeys.Neurosci. Lett. 168, 251–253.PubMedCrossRefGoogle Scholar
  82. Moore DJ, L Zhang, TM Dawson and VL Dawson (2003) A missense mutation (L166P) in DJ-1, linked to familial Parkinson’s disease, confers reduced protein stability and impairs homo-oligomerization.J. Neurochem. 87(6), 1558–1567.PubMedCrossRefGoogle Scholar
  83. Nagakubo D, T Taira, H Kitaura, M Ikeda, K Tamai, SM Iguchi-Ariga and H Ariga (1997) DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras.Biochem. Biophys. Res. Commun. 231(2), 509–513.PubMedCrossRefGoogle Scholar
  84. Neumann M, PJ Kahle, BI Giasson, L Ozmen, E Borroni, W Spooren, V Muller, S Odoy, H Fujiwara, M Hasegawa, T Iwatsubo, JQ Trojanowski, HA Kretzschmar and C Haass (2002) Misfolded proteinase K-resistant hyperphos-phorylated alpha-synuclein in aged transgenic mice with locomotor deterioration and in human alpha-synucle-inopathies.J. Clin. Invest. 110(10), 1429–1439.PubMedGoogle Scholar
  85. Nicklas WJ, I Vyas and RE Heikkila (1985) Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenyl-pyridine, a metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine.Life Sci. 36(26), 2503–2508.PubMedCrossRefGoogle Scholar
  86. Nieto M, FJ Gil-Bea, E Dalfo, M Guadrado, F Cabodevilla, B Sanchez, S Catena, T Sesma, E Ribe, I Ferrer, MJ Ramirez and T Gomez-Isla (2006) Increased sensitivity to MPTP in human alpha-synuclein A30P transgenic mice.Neurobiol. Aging 27(6), 848–856.PubMedCrossRefGoogle Scholar
  87. Paisan-Ruiz C, S Jain, EW Evans, WP Gilks, J Simon, M van der Brug, A Lopez de Munain, S Aparicio, AM Gil, N Khan, J Johnson, JR Martinez, D Nicholl, IM Carrera, AS Pena, R de Silva, A Lees, JF Marti-Masso, J Perez-Tur, NW Wood and AB Singleton (2004) Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease.Neuron 44(4), 595–600.PubMedCrossRefGoogle Scholar
  88. Palacino JJ, D Sagi, MS Goldberg, S Krauss, C Motz, M Wacker, J Klose and J Shen (2004) Mitochondrial dys- function and oxidative damage in parkin-deficient mice.J. Biol. Chem. 279(18), 18614–18622.PubMedCrossRefGoogle Scholar
  89. Parker WD Jr, S J Boyson and JK Parks (1989) Abnormalities of the electron transport chain in idiopathic Parkinson’s disease.Ann. Neurol. 26(6), 719–723.PubMedCrossRefGoogle Scholar
  90. Peng J, XO Mao, FF Stevenson, M Hsu and JK Andersen (2004) The herbicide paraquat induces dopaminergic nigral apoptosis through sustained activation of the JNK pathway.J. Biol. Chem. 279(31), 32626–32632. Epub 2004 May 20.PubMedCrossRefGoogle Scholar
  91. Perez FA and RD Palmiter (2005) Parkin-deficient mice are not a robust model of parkinsonism.Proc. Natl. Acad. Sci. USA 102(6), 2174–2179.PubMedCrossRefGoogle Scholar
  92. Perez FA, WR Curtis and RD Palmiter (2005) Parkin-deficient mice are not more sensitive to 6-hydroxydopamine or methamphetamine neurotoxicity.BMC Neurosci. 6, 71.PubMedCrossRefGoogle Scholar
  93. Perry TL, VW Yong, RA Wall and K Jones (1986) Paraquat and two endogenous analogues of the neurotoxic substance N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine do not damage dopaminergic nigrostriatal neurons in the mouse.Neurosci. Lett. 69(3), 285–289.PubMedCrossRefGoogle Scholar
  94. Petroske E, GE Meredith, S Callen, S Totterdell and YS Lau (2001) Mouse model of Parkinsonism, a comparison between subacute MPTP and chronic MPTP/probenecid treatment.Neuroscience 106(3), 589–601.PubMedCrossRefGoogle Scholar
  95. Pezzella A, M d’Ischia, A Napolitano, G Misuraca and G Prota (1997) Iron-mediated generation of the neurotoxin 6-hydroxydopamine quinone by reaction of fatty acid hydroperoxides with dopamine, a possible contributory mechanism for neuronal degeneration in Parkinson’s disease.J. Med. Chem. 40(14), 2211–2216.PubMedCrossRefGoogle Scholar
  96. Polymeropoulos MH, C Lavedan, E Leroy, SE Ide, A Dehejia, A Dutra, B Pike, H Root, J Rubenstein, R Boyer, ES Stenroos, S Chandrasekharappa, A Athanassiadou, T Papapetropoulos, WG Johnson, AM Lazzarini, RC Duvoisin, G Di Iorio, LI Golbe and RL Nussbaum (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease.Science 276(5321), 2045–2047.PubMedCrossRefGoogle Scholar
  97. Pramstaller PP, MG Schlossmacher, TS Jacques, F Scaravilli, C Eskelson, I Pepivani, K Hedrich, S Adel, M Gonzales-McNeal, R Hilker, PL Kramer and C Klein (2005) Lewy body Parkinson’s disease in a large pedigree with 77 Parkin mutation carriers.Ann. Neurol. 58(3), 411–422.PubMedCrossRefGoogle Scholar
  98. Purisai MG, AL McCormack, S Cumine, J Li, MZ Isla and DA Di Monte (2007) Microglial activation as a priming event leading to paraquat-induced dopaminergic cell degeneration.Neurobiol. Dis. 25(2), 392–400.PubMedCrossRefGoogle Scholar
  99. Purisai MG, AL McCormack, JW Langston, LC Johnston and DA Di Monte (2005) Alpha-synuclein expression in the substantia nigra of MPTP-lesioned non-human primates.Neurobiol. Dis. 20(3), 898–906.PubMedCrossRefGoogle Scholar
  100. Qin L, X Wu, ML Block, Y Liu, GR Breese, JS Hong, DJ Knapp and FT Crews (2007) Systemic LPS causes chronic neuroinflammation and progressive neurodegen-eration.Glia 55(5), 453–462.PubMedCrossRefGoogle Scholar
  101. Rajput A, DW Dickson, CA Robinson, OA Ross, JC Dachsel, SJ Lincoln, SA Cobb, ML Rajput and MJ Farrer (2006) Parkinsonism, Lrrk2 G’S, and tau neuropa-thology.Neurology 67(8), 1506–1508.PubMedCrossRefGoogle Scholar
  102. Ramsay RR and TP Singer (1986) Energy-dependent uptake of N-methyl-4-phenylpyridinium, the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, by mitochondria.J. Biol. Chem. 261(17), 7585–7587.PubMedGoogle Scholar
  103. Ramsden DB, RB Parsons, SL Ho and RH Waring (2001) The aetiology of idiopathic Parkinson’s disease.Mol. Pathol. 54(6), 369–380.PubMedGoogle Scholar
  104. Rathke-Hartlieb S, PJ Kahle, M Neumann, L Ozmen, S Haid, M Okochi, C Haas and JB Schulz (2001) Sensitivity to MPTP is not increased in Parkinson’s disease-associated mutant alpha-synuclein transgenic mice.J. Neurochem. 77(4), 1181–1184.PubMedCrossRefGoogle Scholar
  105. Richardson JR, WM Caudle, TS Guillot, JL Watson, E Nakamaru-Ogiso, BB Seo, TB Sherer, JT Greenamyre, T Yagi, A Matsuno-Yagi and GW Miller (2007) Obligatory role for complex I inhibition in the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).Toxicol. Sci. 95(1), 196–204.PubMedCrossRefGoogle Scholar
  106. Richardson JR, Y Quan, TB Sherer, JT Greenamyre and GW Miller (2005) Paraquat neurotoxicity is distinct from that of MPTP and rotenone.Toxicol. Sci. 88(1), 193–201.PubMedCrossRefGoogle Scholar
  107. Richfield EK, MJ Thiruchelvam, DA Cory-Slechta, C Wuertzer, RR Gainetdinov, MG Caron, DA Di Monte and HJ Federoff (2002) Behavioral and neurochemical effects of wild-type and mutated human alpha-synuclein in transgenic mice.Exp. Neurol. 175(1), 35–48.PubMedCrossRefGoogle Scholar
  108. Richter F, M Hamann and A Richter (2007) Chronic rotenone treatment induces behavioral effects but no pathological signs of parkinsonism in mice.J. Neurosci. Res. 85(3), 681–691.PubMedCrossRefGoogle Scholar
  109. Riess O, R Kruger, H Hochstrasser, AS Soehn, S Nuber, T Franck and D Berg (2006) Genetic causes of Parkinson’s disease, extending the pathway.J. Neural Transm. Suppl.70, 181–189.CrossRefGoogle Scholar
  110. Rockenstein E, M Mallory, M Hashimoto, D Song, CW Shults, I Lang and E Masliah (2002) Differential neuropathological alterations in transgenic mice expressing alpha-synuclein from the platelet-derived growth factor and Thy-1 promoters.J. Neurosci. Res. 68(5), 568–578.PubMedCrossRefGoogle Scholar
  111. Sanchez-Ramos JR, F Hefti and WJ Weiner (1987) Paraquat and Parkinson’s disease.Neurology 37(4), 728.PubMedGoogle Scholar
  112. Sasaki S, A Shirata, K Yamane and M Iwata (2004) Parkin-positive autosomal recessive juvenile Parkinsonism with alpha-synuclein-positive inclusions.Neurology 63(4), 678–82.PubMedGoogle Scholar
  113. Schapira AH (1994) Evidence for mitochondrial dysfunction in Parkinson’s disease - a critical appraisal.Mov. Disord. 9, 125–138.PubMedCrossRefGoogle Scholar
  114. Schapira AH, JM Cooper, D Dexter, JB Clark, P Jenner and CD Marsden (1990) Mitochondrial complex I deficiency in Parkinson’s disease.J. Neurochem. 54(3), 823–827.PubMedCrossRefGoogle Scholar
  115. Schluter OM, F Fornai, MG Alessandri, S Takamori, M Geppert, R Jahn and TC Sudhof (2003) Role of alpha-synuclein in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyri-dine-induced parkinsonism in mice.Neuroscience 118, 985–1002.PubMedCrossRefGoogle Scholar
  116. Sechi GP, V Agnetti, M Piredda, M Canu, F Deserra, HA Omar and G Rosati. (1992) Acute and persistent parkinsonism after use of diquat.Neurology 42(1), 261–263.PubMedGoogle Scholar
  117. Segura Aguilar J and RM Kostrzewa (2004) Neurotoxins and neurotoxic species implicated in neurodegeneration.Neurotox. Res. 6(7–8), 615–630.CrossRefGoogle Scholar
  118. Shang H, D Lang, B Jean-Marc and A Kaelin-Lang (2004) Localization of DJ-1 mRNA in the mouse brain.Neurosci. Lett. 367(3), 273–277.PubMedCrossRefGoogle Scholar
  119. Shendelman S, A Jonason, C Martinat, T Leete and A Abeliovich (2004) DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formation.PLoS Biol. 2(11), e362.CrossRefGoogle Scholar
  120. Shepherd KR, ES Lee, L Schmued, Y Jiao, SF Ali, ET Oriaku, NS Lamango, KF Soliman and CG Charlton (2006) The potentiating effects of 1-methyl-4-phe-nyl-1,2,3,6-tetrahydropyridine (MPTP) on paraquat-induced neurochemical and behavioral changes in mice.Pharmacol. Biochem. Behav. 83(3), 349–359.PubMedCrossRefGoogle Scholar
  121. Sherer TB, JH Kim, R Betarbet and JT Greenamyre (2003) Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and alpha-synuclein aggregation.Exp. Neurol. 179(1), 9–16.PubMedCrossRefGoogle Scholar
  122. Shimizu K, K Ohtaki, K Matsubara, K Aoyama, T Uezono, O Saito, M Suno, K Ogawa, N Hayase, K Kimura and H Shiono (2001) Carrier-mediated processes in blood-brain barrier penetration and neural uptake of paraquat.Brain Res. 906(1–2), 135–142.PubMedCrossRefGoogle Scholar
  123. Singleton AB, M Farrer, J Johnson, A Singleton, S Hague, J Kachergus, M Hulihan, T Peuralinna, A Dutra, R Nussbaum, S Lincoln, A Crawley, M Hanson, D Maraganore, C Adler, MR Cookson, M Muenter, M Baptista, D Miller, J Blancato, J Hardy and K Gwinn-Hardy (2003) α-Synuclein locus triplication causes Parkinson’s disease.Science 302(5646), 841.PubMedCrossRefGoogle Scholar
  124. Song DD, CW Shults, A Sisk, E Rockenstein and E Masliah (2004) Enhanced substantia nigra mitochondrial pathology in human α-synuclein transgenic mice after treatment with MPTP.Exp. Neurol. 186(2), 158–172.PubMedCrossRefGoogle Scholar
  125. Spillantini MG, RA Crowther, R Jakes, M Hasegawa and M Goedert (1998) α-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with lewy bodies.Proc. Natl. Acad. Sci. USA 95(11), 6469–6473.PubMedCrossRefGoogle Scholar
  126. Spira PJ, DM Sharpe, G Halliday, J Cavanagh and GA Nicholson (2001) Clinical and pathological features of a Parkinsonian syndrome in a family with an Ala53Thr alpha-synuclein mutation.Ann. Neurol. 49(3), 313–319.PubMedCrossRefGoogle Scholar
  127. Taira T, Y Saito, T Niki, SM Iguchi-Ariga, K Takahashi and H Ariga (2004) DJ-1 has a role in antioxidative stress to prevent cell death.EMBO Rep. 5(2), 213–218.PubMedCrossRefGoogle Scholar
  128. Thiffault C, JW Langston and DA Di Monte (2000) Increased striatal dopamine turnover following acute administration of rotenone to mice.Brain Res. 885, 283–288.PubMedCrossRefGoogle Scholar
  129. Thiruchelvam M, A McCormack, EK Richfield, RB Baggs, AW Tank, DA Di Monte and DA Cory-Slechta (2003) Age-related irreversible progressive nigrostriatal dopaminergic neurotoxicity in the paraquat and maneb model of the Parkinson’s disease phenotype.Eur. J. Neurosci. 18(3), 589–600.PubMedCrossRefGoogle Scholar
  130. Thiruchelvam M, EK Richfield, RB Baggs, AW Tank and DA Cory-Slechta (2000) The nigrostriatal dopaminergic system as a preferential target of repeated exposures to combined paraquat and maneb, implications for Parkinson’s disease.J. Neurosci. 20(24), 9207–9214.PubMedGoogle Scholar
  131. Thiruchelvam MJ, JM Powers, DA Cory-Slechta and EK Richfield (2004) Risk factors for dopaminergic neuron loss in human alpha-synuclein transgenic mice.Eur. J. Neurosci. 19(4), 845–854.PubMedCrossRefGoogle Scholar
  132. Tofaris GK, P Garcia Reitbock, T Humby, SL Lambourne, M O’Connell, B Ghetti, H Gossage, PC Emson, LS Wilkinson, M Goedert and MG Spillantini (2006) Pathological changes in dopaminergic nerve cells of the substantia nigra and olfactory bulb in mice transgenic for truncated human alpha-synuclein(1–120), implications for Lewy body disorders.J. Neurosci. 26(15), 3942–3950.PubMedCrossRefGoogle Scholar
  133. Valente EM, S Salvi, T Ialongo, R Marongiu, AE Elia, V Caputo, L Romito, A Albanese, B Dallapiccola and AR Bentivoglio (2004) PINK1 mutations are associated with sporadic early-onset parkinsonism.Ann. Neurol. 56(3), 336–341.PubMedCrossRefGoogle Scholar
  134. van der Putten H, KH Wiederhold, A Probst, S Barbieri, C Mistl, S Danner, S Kauffmann, K Hofele, WP Spooren, MA Ruegg, S Lin, P Caroni, B Sommer, M Tolnay and G Bilbe (2000) Neuropathology in mice expressing human alpha-synuclein.J. Neurosci. 20(16), 6021–6029.PubMedGoogle Scholar
  135. Vila M, S Vukosavic, V Jackson-Lewis, M Neystat, M Jakowec and S Przedborski (2000) Alpha-synuclein up-regulation in substantia nigra dopaminergic neurons following administration of the parkinsonian toxin MPTP.J. Neurochem. 74(2), 721–729.PubMedCrossRefGoogle Scholar
  136. Von Coelln R, B Thomas, JM Savitt, KL Lim, M Sasaki, EJ Hess, VL Dawson and TM Dawson (2004) Loss of locus coeruleus neurons and reduced startle in parkin null mice.Proc. Natl. Acad. Sci. USA 101(29), 10744–10749.CrossRefGoogle Scholar
  137. Wakamatsu M, A Ishii, S Iwata, J Sakagami, Y Ukai, M Ono, D Kanbe, SL Muramatsu, K Kobayashi, T Iwatsubo and M Yoshimoto (2006) Selective loss of nigral dopamine neurons induced by over-expression of truncated human α-synuclein in mice.Neurobiol Aging 2006 Dec 13; [Epub ahead of print]Google Scholar
  138. Walters TL, I Irwin, K Delfani, JW Langston and AM Janson (1999) Diethyldithiocarbamate causes nigral cell loss and dopamine depletion with nontoxic doses of MPTP.Exp. Neurol. 156(1), 62–70.PubMedCrossRefGoogle Scholar
  139. Widdowson PS, MJ Farnworth, R Upton and MG Simpson (1996) No changes in behaviour, nigro-striatal system neurochemistry or neuronal cell death following toxic multiple oral paraquat administration to rats.Hum. Exp. Toxicol. 15, 583–591.PubMedCrossRefGoogle Scholar
  140. Wintermeyer P, R Kruger, W Kuhn, T Muller, D Woitalla, D Berg, G Becker, E Leroy, M Polymeropoulos, K Berger, H Przuntek, L Schols, JT Epplen and O Riess (2000) Mutation analysis and association studies of the UCHL1 gene in German Parkinson’s disease patients.Neuroreport 11(10), 2079–2082.PubMedCrossRefGoogle Scholar
  141. Xu J, N Zhong, H Wang, JE Elias, CY Kim, I Woldman, C Pifl, SP Gygi, C Geula and BA Yankner (2005) The Parkinson’s disease-associated DJ-1 protein is a transcriptional co-activator that protects against neuronal apoptosis.Hum. Mol. Genet. 14(9), 1231–1241.PubMedCrossRefGoogle Scholar
  142. Xu K, E Bastia and M Schwarzschild (2005) Therapeutic potential of adenosine A(2A) receptor antagonists in Parkinson’s disease.Pharmacol. Ther. 105(3), 267–310.PubMedCrossRefGoogle Scholar
  143. Yoshino H, Y Nakagawa-Hattori, T Kondo and Y Mizuno (1992) Mitochondrial complex I and II activities of lymphocytes and platelets in Parkinson’s disease.J. Neural Transm. Park. Dis. Dement. Sect. 4(1), 27–34.PubMedCrossRefGoogle Scholar
  144. Youdim MB and P Riederer (1993) The role of iron in senescence of dopaminergic neurons in Parkinson’s disease.J. Neural Transm. Suppl.40, 57–67.Google Scholar
  145. Zarranz JJ, J Alegre, JC Gomez-Esteban, E Lezcano, R Ros, I Ampuero, L Vidal, J Hoenicka, O Rodriguez, B Atares, V Llorens, E Gomez Tortosa, T del Ser, DG Munoz and JG de Yebenes (2004) The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia.Ann. Neurol. 55(2), 164–173.PubMedCrossRefGoogle Scholar
  146. Zhang J, Y Song, H Chen and D Fan (2005) The tau gene haplotype h1 confers a susceptibility to Parkinson’s disease.Eur. Neurol. 53(1), 15–21.PubMedCrossRefGoogle Scholar
  147. Zhang W, T Wang, Z Pei, DS Miller X Wu, ML Block, B Wilson, W Zhang, Y Zhou, JS Hong and J Zhang (2005) Aggregated alpha-synuclein activates microglia, a process leading to disease progression in Parkinson’s disease.FASEB J. 19(6), 533–542.PubMedCrossRefGoogle Scholar
  148. Zhou W and CR Freed (2005) DJ-1 up-regulates glutathione synthesis during oxidative stress and inhibits A53T alpha-synuclein toxicity.J. Biol. Chem. 280(52), 43150–43158.PubMedCrossRefGoogle Scholar
  149. Zhou W, M Zhu, MA Wilson, GA Petsko and AL Fink (2006) The oxidation state of DJ-1 regulates its chaperone activity toward alpha-synuclein.J. Mol. Biol. 356(4), 1036–1048.PubMedCrossRefGoogle Scholar
  150. Zhu C, P Vourc’h, PO Fernagut, SM Fleming, S Lacan, CD Dicarlo, RL Seaman and MF Chesselet (2004) Variable effects of chronic subcutaneous administration of rote-none on striatal histology.J. Comp. Neurol. 478(4), 418–426.PubMedCrossRefGoogle Scholar
  151. Zimprich A, S Biskup, P Leitner, P Lichtner, M Farrer, S Lincoln, J Kachergus, M Hulihan, RJ Uitti, DB Calne, AJ Stoessl, RF Pfeiffer, N Patenge, IC Carbajal, P Vieregge, F Asmus, B Muller-Myhsok, DW Dickson, T Meitinger, TM Strom, ZK Wszolek and T Gasser (2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology.Neuron 44(4), 601–607.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  1. 1.The Parkinson’s InstituteSunnyvaleUSA

Personalised recommendations