Skip to main content
Log in

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

  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Alam M and WJ Schmidt (2002) Rotenone destroys dopa- minergic neurons and induces parkinsonian symptoms in rats.Behav. Brain Res. 136(1), 317–324.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Chung KK and TM Dawson (2004) Parkin and Hsp70 sacked by BAG5.Neuron 44(6), 899–901.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    CAS  Google Scholar 

  • 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]

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Galvin JE, VM Lee and JQ Trojanowski (2001) Synuclein-opathies, clinical and pathological implications.Arch. Neurol. 58(2), 186–190.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Guilarte TR (2001) Is methamphetamine abuse a risk factor in parkinsonism?Neurotoxicology 22(6), 725–731.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Langston JW (2006) The Parkinson’s complex, parkinsonism is just the tip of the iceberg.Ann. Neurol. 59(4), 591–6.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Ramsden DB, RB Parsons, SL Ho and RH Waring (2001) The aetiology of idiopathic Parkinson’s disease.Mol. Pathol. 54(6), 369–380.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Sanchez-Ramos JR, F Hefti and WJ Weiner (1987) Paraquat and Parkinson’s disease.Neurology 37(4), 728.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Schapira AH (1994) Evidence for mitochondrial dysfunction in Parkinson’s disease - a critical appraisal.Mov. Disord. 9, 125–138.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Segura Aguilar J and RM Kostrzewa (2004) Neurotoxins and neurotoxic species implicated in neurodegeneration.Neurotox. Res. 6(7–8), 615–630.

    Article  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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]

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Amy B. Manning-BoĞ.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Manning-BoĞ, A.B., Langston, J.W. Model fusion: The next phase in developing animal models for parkinson’s disease. neurotox res 11, 219–240 (2007). https://doi.org/10.1007/BF03033569

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03033569

Keywords

Navigation