Abstract
Rodent models and molecular tools, mainly omics and RNA interference, have been rigorously used to decode the intangible etiology and pathogenesis of Parkinson’s disease (PD). Although convention of contemporary molecular techniques and multiple rodent models paved imperative leads in deciphering the role of putative causative factors and sequential events leading to PD, complete and clear-cut mechanisms of pathogenesis are still hard to pin down. The current article reviews the implications and pros and cons of rodent models and molecular tools in understanding the molecular and cellular bases of PD pathogenesis based on the existing literature. Probable rationales for short of comprehensive leads and future possibilities in spite of the extensive applications of molecular tools and rodent models have also been discussed.
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Parkinson J (2002) An essay on the shaking palsy 1817. J Neuropsychiatry Clin Neurosci 14:223–236
Goetz CG (1986) Charcot on Parkinson’s disease. Mov Disord 1:27–32
Singh MP, Patel S, Dikshit M, Gupta YK (2006) Contribution of genomics and proteomics in understanding the role of modifying factors in Parkinson’s disease. Indian J Biochem Biophys 43:69–81
Miller RL, James-Kracke M, Sun GY, Sun AY (2009) Oxidative and inflammatory pathways in Parkinson’s disease. Neurochem Res 34:55–65
Wirdefeldt K, Adami HO, Cole P, Trichopoulos D, Mandel J (2011) Epidemiology and etiology of Parkinson’s disease: a review of the evidence. Eur J Epidemiol 26:S1–S58
Klockgether T (2004) Parkinson’s disease: clinical aspects. Cell Tissue Res 318:115–120
Morgan JC, Mehta SH, Sethi KD (2010) Biomarkers in Parkinson’s disease. Curr Neurol Neurosci Rep 10:423–430
Ebin J (1951) Surgical treatment of Parkinsonism: indications and results. Bull N Y Acad Med 27:653–678
Cicchetti F, Drouin-Ouellet J, Gross RE (2009) Environmental toxins and Parkinson’s disease: what have we learned from pesticide-induced animal models? Trends Pharmacol Sci 30:475–483
Singhal NK, Srivastava G, Agrawal S, Jain SK, Singh MP (2012) Melatonin as a neuroprotective agent in the rodent models of Parkinson’s disease: is it all set to irrefutable clinical translation? Mol Neurobiol 45:186–199
Kumar A, Ahmad I, Shukla S, Singh BK, Patel DK, Pandey HP, Singh C (2010) Effect of zinc and paraquat co-exposure on neurodegeneration: modulation of oxidative stress and expression of metallothioneins, toxicant responsive and transporter genes in rats. Free Radic Res 44:950–965
Khalid M, Aoun RA, Mathews TA (2011) Altered striatal dopamine release following a sub-acute exposure to manganese. J Neurosci Methods 202:182–191
Singh AK, Tiwari MN, Upadhyay G, Patel DK, Singh D, Prakash O, Singh MP (2012) Long-term exposure to cypermethrin induces nigrostriatal dopaminergic neurodegeneration in adult rats: postnatal exposure enhances the susceptibility during adulthood. Neurobiol Aging 33:404–415
Betarbet R, Sherer TB, Greenamyre JT (2002) Animal models of Parkinson’s disease. Bioessays 24:308–318
Thiruchelvam M, Brockel BJ, Richfield EK, Baggs RB, Cory-Slechta DA (2000) Potentiated and preferential effects of combined paraquat and maneb on nigrostriatal dopamine systems: environmental risk factors for Parkinson’s disease? Brain Res 873:225–234
Langston JW, Ballard P, Tetrud JW, Irwin I (1983) Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219:979–980
Patel S, Singh V, Kumar A, Gupta YK, Singh MP (2006) Status of antioxidant defense system and expression of toxicant responsive genes in striatum of maneb and paraquat-induced Parkinson’s disease phenotype in mouse: mechanism of neurodegeneration. Brain Res 108:9–18
Gorell JM, Johnson CC, Rybicki BA, Peterson EL, Kortsha GX, Brown GG, Richardson RJ (1999) Occupational exposure to manganese, copper, lead, iron, mercury and zinc and the risk of Parkinson’s disease. Neurotoxicology 20:239–247
Singh AK, Tiwari MN, Dixit A, Upadhyay G, Patel DK, Singh D, Prakash O, Singh MP (2011) Nigrostriatal proteomics of cypermethrin-induced dopaminergic neurodegeneration: microglial activation dependent and independent regulations. Toxicol Sci 122:526–538
Srivastava G, Dixit A, Yadav S, Patel DK, Prakash O, Singh MP (2012) Resveratrol potentiates cytochrome P450 2d22-mediated neuroprotection in maneb- and paraquat-induced parkinsonism in the mouse. Free Radic Biol Med 52:1294–1306
Srivastava G, Singh K, Tiwari MN, Singh MP (2010) Proteomics in Parkinson’s disease: current trends, translational snags and future possibilities. Expert Rev Proteomics 7:127–139
Srivastava G, Dixit A, Prakash O, Singh MP (2011) Tiny non-coding RNAs in Parkinson’s disease: Implications, expectations and hypes. Neurochem Int 59:759–769
Klein C, Schlossmacher MG (2007) Parkinson disease, 10 years after its genetic revolution: multiple clues to a complex disorder. Neurology 69:2093–2104
Gao HM, Hong JS (2011) Gene–environment interactions: key to unraveling the mystery of Parkinson’s disease. Prog Neurobiol 94:1–19
Uversky VN (2004) Neurotoxicant-induced animal models of Parkinson’s disease: understanding the role of rotenone, maneb and paraquat in neurodegeneration. Cell Tissue Res 318:225–241
Ginsberg SD, Mirnics K (2006) Functional genomic methodologies. Prog Brain Res 158:15–40
Shilling PD, Kelsoe JR (2002) Functional genomics approaches to understanding brain disorders. Pharmacogenomics 3:31–45
Vargas RH, Ornelas LF, González IL, Escovar JR, Zurita M, Reynaud E (2011) Synphilin suppresses α-synuclein neurotoxicity in a Parkinson’s disease Drosophila model. Genesis 49:392–402
Ramsden DB, Parsons RB, Ho SL, Waring RH (2001) The aetiology of idiopathic Parkinson’s disease. Mol Pathol 54:369–380
Migliore L, Coppede F (2009) Environmental-induced oxidative stress in neurodegenerative disorders and aging. Mutat Res 674:73–84
Wood-Kaczmar A, Gandhi S, Wood NW (2006) Understanding the molecular causes of Parkinson’s disease. Trends Mol Med 12:521–528
Bove J, Prou D, Perier C, Przedborski S (2005) Toxin-induced models of Parkinson’s disease. NeuroRx 2:484–494
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 60:197–203
He Y, Appel S, Le W (2001) Minocycline inhibits microglial activation and protects nigral cells after 6-hydroxydopamine injection into mouse striatum. Brain Res 909:187–193
Silva RM, Ries V, Oo TF, Yarygina O, Jackson-Lewis V, Ryu EJ, Lu PD, Marciniak SJ, Ron D, Przedborski S, Kholodilov N, Greene LA, Burke RE (2005) CHOP/GADD153 is a mediator of apoptotic death in substantia nigra dopamine neurons in an in vivo neurotoxin model of parkinsonism. J Neurochem 95:974–986
Reyes S, Mitrofanis J (2008) Patterns of FOS expression in the spinal cord and periaqueductal grey matter of 6OHDA-lesioned rats. Int J Neurosci 118:1053–1079
Latchoumycandane C, Anantharam V, Jin H, Kanthasamy A, Kanthasamy A (2011) Dopaminergic neurotoxicant (2011) 6-OHDA induces oxidative damage through proteolytic activation of PKCδ in cell culture and animal models of Parkinson’s disease. Toxicol Appl Pharmacol 256:314–323
Bernstein AI, Garrison SP, Zambetti GP, O’Malley KL (2011) 6-OHDA generated ROS induces DNA damage and p53- and PUMA-dependent cell death. Mol Neurodegener 6:2
Proft J, Faraji J, Robbins JC, Zucchi FC, Zhao X, Metz GA, Braun JE (2011) Identification of bilateral changes in TID1 expression in the 6-OHDA rat model of Parkinson’s disease. PLoS One 6:e26045
Przedborski S, Vila M (2003) The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model: a tool to explore the pathogenesis of Parkinson’s disease. Ann N Y Acad Sci 991:189–198
Ross CA, Smith WW (2007) Gene-environment interactions in Parkinson’s disease. Parkinsonism Relat Disord 13:S309–S315
Cui M, Aras R, Christian WV, Rappold PM, Hatwar M, Panza J, Jackson-Lewis V, Javitch JA, Ballatori N, Przedborski S, Tieu K (2009) The organic cation transporter-3 is a pivotal modulator of neurodegeneration in the nigrostriatal dopaminergic pathway. Proc Natl Acad Sci U S A 106:8043–8048
Karunakaran S, Saeed U, Mishra M, Valli RK, Joshi SD, Meka DP, Seth P, Ravindranath V (2008) Selective activation of p38 mitogen-activated protein kinase in dopaminergic neurons of substantia nigra leads to nuclear translocation of p53 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice. J Neurosci 28:12500–12509
Castro-Caldas M, Carvalho AN, Rodrigues E, Henderson C, Wolf CR, Gama MJ (2012) Glutathione S-transferase pi mediates MPTP-induced c-Jun N-terminal kinase activation in the nigrostriatal pathway. Mol Neurobiol. doi:10.1007/s12035-012-8266-9
Zawada WM, Banninger GP, Thornton J, Marriott B, Cantu D, Rachubinski AL, Das M, Griffin WS, Jones SM (2011) Generation of reactive oxygen species in 1-methyl-4-phenylpyridinium (MPP+) treated dopaminergic neurons occurs as an NADPH oxidase-dependent two-wave cascade. J Neuroinflammation 8:129
Durgadoss L, Nidadavolu P, Valli RK, Saeed U, Mishra M, Seth P, Ravindranath V (2012) Redox modification of Akt mediated by the dopaminergic neurotoxin MPTP, in mouse midbrain, leads to down-regulation of pAkt. FASEB J 26:1473–1483
Jeong HJ, Kim DW, Woo SJ, Kim HR, Kim SM, Jo HS, Park M, Kim DS, Kwon OS, Hwang IK, Han KH, Park J, Eum WS, Choi SY (2012) Transduced Tat-DJ-1 protein protects against oxidative stress-induced SH-SY5Y cell death and Parkinson disease in a mouse model. Mol Cells. doi:10.1007/s10059-012-2255-8
Martin HL, Mounsey RB, Mustafa S, Sathe K, Teismann P (2012) Pharmacological manipulation of peroxisome proliferator-activated receptor γ (PPARγ) reveals a role for anti-oxidant protection in a model of Parkinson’s disease. Exp Neurol 235:528–538
Park HK, Cho AR, Lee SC, Ban JY (2012) MPTP-induced model of Parkinson’s disease in heat shock protein 70.1 knockout mice. Mol Med Report 5:1465–1468
Domenger D, Dea D, Theroux L, Moquin L, Gratton A, Poirier J (2012) The MPTP neurotoxic lesion model of Parkinson’s disease activates the apolipoprotein E cascade in the mouse brain. Exp Neurol 233:513–522
Airavaara M, Harvey BK, Voutilainen MH, Shen H, Chou J, Lindholm P, Lindahl M, Tuominen RK, Saarma M, Wang Y, Hoffer B (2011) CDNF protects the nigrostriatal dopamine system and promotes recovery after MPTP treatment in mice. Cell Transplant. doi:10.3727/096368911X600948
Bezard E, Przedborski S (2011) A tale on animal models of Parkinson’s disease. Mov Disord 26:993–1002
LoPachin RM, Gavin T (2008) Response to “Paraquat: the red herring of Parkinson’s disease research”. Toxicol Sci 103:219–221
Shimizu K, Ohtaki K, Matsubara K, Aoyama K, Uezono T, Saito O, Suno M, Ogawa K, Hayase N, Kimura K, Shiono H (2001) Carrier-mediated processes in blood–brain barrier penetration and neural uptake of paraquat. Brain Res 906:135–142
Feng LR, Maguire-Zeiss KA (2011) Dopamine and paraquat enhance α-synuclein-induced alterations in membrane conductance. Neurotox Res 20:387–401
Miller RL, Sun GY, Sun AY (2007) Cytotoxicity of paraquat in microglial cells: involvement of PKCdelta- and ERK1/2-dependent NADPH oxidase. Brain Res 1167:129–139
Huang CL, Lee YC, Yang YC, Kuo TY, Huang NK (2012) Minocycline prevents paraquat-induced cell death through attenuating endoplasmic reticulum stress and mitochondrial dysfunction. Toxicol Lett 209:203–210
Rappold PM, Cui M, Chesser AS, Tibbett J, Grima JC, Duan L, Sen N, Javitch JA, Tieu K (2011) Paraquat neurotoxicity is mediated by the dopamine transporter and organic cation transporter-3. Proc Natl Acad Sci U S A 108:20766–20771
Fei Q, Ethell DW (2008) Maneb potentiates paraquat neurotoxicity by inducing key Bcl-2 family members. J Neurochem 105:2091–2097
Litteljohn D, Nelson E, Bethune C, Hayley S (2011) The effects of paraquat on regional brain neurotransmitter activity, hippocampal BDNF and behavioural function in female mice. Neurosci Lett 502:186–191
Kachroo A, Irizarry MC, Schwarzschild MA (2010) Caffeine protects against combined paraquat and maneb-induced dopaminergic neuron degeneration. Exp Neurol 223:657–661
Wang A, Costello S, Cockburn M, Zhang X, Bronstein J, Ritz B (2011) Parkinson’s disease risk from ambient exposure to pesticides. Eur J Epidemiol 26:547–555
Kang H, Han BS, Kim SJ, Oh YJ (2012) Mechanisms to prevent caspase activation in rotenone-induced dopaminergic neurodegeneration: role of ATP depletion and procaspase-9 degradation. Apoptosis 17:449–462
Shin EJ, Kim EM, Lee JA, Rhim H, Hwang O (2012) Matrix metalloproteinase-3 is activated by HtrA2/Omi in dopaminergic cells: relevance to Parkinson’s disease. Neurochem Int 60:249–256
Meredith GE, Sonsalla PK, Chesselet MF (2008) Animal models of Parkinson’s disease progression. Acta Neuropathol 115:385–398
Ritz BR, Manthripragada AD, Costello S, Lincoln SJ, Farrer MJ, Cockburn M, Bronstein J (2009) Dopamine transporter genetic variants and pesticides in Parkinson’s disease. Environ Health Perspect 117:964–969
Moretto A, Colosio C (2011) Biochemical and toxicological evidence of neurological effects of pesticides: the example of Parkinson’s disease. Neurotoxicology 32:383–391
Singh AK, Tiwari MN, Prakash O, Singh MP (2012) A current review of cypermethrin-induced neurotoxicity and nigrostriatal dopaminergic neurodegeneration. Curr Neuropharmacol 10:64–71
Sharma H, Zhang P, Barber DS, Liu B (2010) Organochlorine pesticides dieldrin and lindane induce cooperative toxicity in dopaminergic neurons: role of oxidative stress. Neurotoxicology 31:215–222
Cass W (1996) GDNF selectively protects dopamine neurons over serotonin neurons against the neurotoxic effects of methamphetamine. J Neurosci 16:8132–8139
Howard CD, Keefe KA, Garris PA, Daberkow DP (2011) Methamphetamine neurotoxicity decreases phasic, but not tonic, dopaminergic signaling in the rat striatum. J Neurochem 118:668–676
Morrow BA, Roth RH, Redmond DE, Elsworth JD (2011) Impact of methamphetamine on dopamine neurons in primates is dependent on age: implications for development of Parkinson’s disease. Neuroscience 189:277–285
Callaghan RC, Cunningham JK, Sykes J, Kish SJ (2012) Increased risk of Parkinson’s disease in individuals hospitalized with conditions related to the use of methamphetamine or other amphetamine-type drugs. Drug Alcohol Depend 120:35–40
Kousik SM, Graves SM, Napier TC, Zhao C, Carvey PM (2011) Methamphetamine-induced vascular changes lead to striatal hypoxia and dopamine reduction. Neuroreport 22:923–928
Brar S, Henderson D, Schenck J, Zimmerman EA (2009) Iron accumulation in the substantia nigra of patients with Alzheimer disease and parkinsonism. Arch Neurol 66:371–374
Jomova K, Valko M (2011) Advances in metal-induced oxidative stress and human disease. Toxicology 283:65–87
Kienzl E, Puchinger L, Jellinger K, Linert W, Stachelberger H, Jameson RF (1995) The role of transition metals in the pathogenesis of Parkinson’s disease. J Neurol Sci 134:69–78
Kumar A, Singh BK, Ahmad I, Shukla S, Patel DK, Srivastava G, Kumar V, Pandey HP, Singh C (2012) Involvement of NADPH oxidase and glutathione in zinc-induced dopaminergic neurodegeneration in rats: similarity with paraquat neurotoxicity. Brain Res 1438:48–64
Gash DM, Rutland K, Hudson NL, Sullivan PG, Bing G, Cass WA, Pandya JD, Liu M, Choi DY, Hunter RL, Gerhardt GA, Smith CD, Slevin JT, Prince TS (2008) Trichloroethylene: parkinsonism and complex 1 mitochondrial neurotoxicity. Ann Neurol 63:184–192
Holtcamp W (2012) The emerging science of BMAA: do cyanobacteria contribute to neurodegenerative disease? Environ Health Perspect 120:A110–A116
Lannuzel A, Michel PP, Höglinger GU, Champy P, Jousset A, Medja F, Lombès A, Darios F, Gleye C, Laurens A, Hocquemiller R, Hirsch EC, Ruberg M (2003) The mitochondrial complex I inhibitor annonacin is toxic to mesencephalic dopaminergic neurons by impairment of energy metabolism. Neuroscience 121:287–296
Storch A, Ott S, Hwang YI, Ortmann R, Hein A, Frenzel S, Matsubara K, Ohta S, Wolf HU, Schwarz J (2002) Selective dopaminergic neurotoxicity of isoquinoline derivatives related to Parkinson’s disease: studies using heterologous expression systems of the dopamine transporter. Biochem Pharmacol 63:909–920
Ohta S, Tachikawa O, Makino Y, Tasaki Y, Hirobe M (1990) Metabolism and brain accumulation of tetrahydroisoquinoline (TIQ) a possible parkinsonism inducing substance, in an animal model of a poor debrisoquine metabolizer. Life Sci 46:599–605
Mohajjel Nayebi AA, Sheidaei H (2010) Buspirone improves haloperidol-induced Parkinson disease in mice through 5-HT(1A) recaptors. Daru 18:41–45
McNaught KS, Perl DP, Brownell AL, Olanow CW (2004) Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson’s disease. Ann Neurol 56:149–162
Panneton WM, Kumar VB, Gan Q, Burke WJ, Galvin JE (2010) The neurotoxicity of DOPAL: behavioral and stereological evidence for its role in Parkinson disease pathogenesis. PLoS One 5:e15251
Gasser T (2007) Update on the genetics of Parkinson’s disease. Mov Disord 17:S343–S350
Bekris LM, Mata IF, Zabetian CP (2010) The genetics of Parkinson disease. J Geriatr Psychiatry Neurol 23:228–242
Fujioka S, Wszolek ZK (2012) Update on genetics of parkinsonism. Neurodegener Dis 10:257–260
Terzioglu M, Galter D (2008) Parkinson’s disease: genetic versus toxin-induced rodent models. FEBS J 275:1384–1391
Hisahara S, Shimohama S (2010) Toxin-induced and genetic animal models of Parkinson’s disease. Parkinsons Dis 2011:951709
Manning-Bog AB, Langston JW (2007) Model fusion, the next phase in developing animal models for Parkinson’s disease. Neurotox Res 11:219–240
Boger HA, Granholm AC, McGinty JF, Middaugh LD (2010) A dual-hit animal model for age-related Parkinsonism. Prog Neurobiol 90:217–229
Gao HM, Zhang F, Zhou H, Kam W, Wilson B, Hong JS (2011) Neuroinflammation and α-synuclein dysfunction potentiate each other, drivingchronic progression of neurodegeneration in a mouse model of Parkinson’s disease. Environ Health Perspect 119:807–814
Jakowec MW, Petzinger GM (2004) 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned model of Parkinson’s disease, with emphasis on mice and nonhuman primates. Comp Med 54:497–513
Zhu XR, Maskri L, Herold C, Bader V, Stichel CC, Güntürkün O, Lübbert H (2007) Non-motor behavioural impairments in parkin-deficient mice. Eur J Neurosci 26:1902–1911
Emborg ME (2007) Nonhuman primate models of Parkinson’s disease. ILAR J 48:339–355
Duty S, Jenner P (2011) Animal models of Parkinson’s disease: a source of novel treatments and clues to the cause of the disease. Br J Pharmacol 164:1357–1391
Pienaar IS, Götz J, Feany MB (2010) Parkinson’s disease: insights from non-traditional model organisms. Prog Neurobiol 92:558–571
Antony PM, Diederich NJ, Balling R (2011) Parkinson’s disease mouse models in translational research. Mamm Genome 22:401–419
Chesselet MF, Richter F (2011) Modelling of Parkinson’s disease in mice. Lancet Neurol 10:1108–1118
Potashkin JA, Blume SR, Runkle NK (2010) Limitations of animal models of Parkinson’s disease. Parkinsons Dis 2011:658083
Mellick GD, Silburn PA, Sutherland GT, Siebert GA (2010) Exploiting the potential of molecular profiling in Parkinson’s disease: current practice and future probabilities. Expert Rev Mol Diagn 10:1035–1050
Miller RM, Federoff HJ (2006) Microarrays in Parkinson’s disease: a systematic approach. NeuroRx 3:319–326
Chang XL, Mao XY, Li HH, Zhang JH, Li NN, Burgunder JM, Peng R, Tan EK (2011) Association of GWAS loci with PD in China. Am J Med Genet B Neuropsychiatr Genet 156B:334–339
Biernacka JM, Armasu SM, Cunningham JM, Eric Ahlskog J, Chung SJ, Maraganore DM (2011) Do interactions between SNCA, MAPT, and LRRK2 genes contribute to Parkinson’s disease susceptibility? Parkinsonism Relat Disord 17:730–736
Chung SJ, Armasu SM, Biernacka JM, Lesnick TG, Rider DN, Lincoln SJ, Ortolaza AI, Farrer MJ, Cunningham JM, Rocca WA, Maraganore DM (2011) Common variants in PARK loci and related genes and Parkinson’s disease. Mov Disord 26:280–288
Autere J, Moilanen JS, Finnila S, Soininen H, Mannermaa A, Hartikainen P, Hallikainen M, Majamaa K (2004) Mitochondrial DNA polymorphisms as risk factors for Parkinson’s disease and Parkinson’s disease dementia. Hum Genet 115:29–35
Simunovic F, Yi M, Wang Y, Macey L, Brown LT, Krichevsky AM, Andersen SL, Stephens RM, Benes FM, Sonntag KC (2009) Gene expression profiling of substantia nigra dopamine neurons: further insights into Parkinson’s disease pathology. Brain 132:1795–1809
Grunblatt E, Mandel S, Jacob-Hirsch J, Zeligson S, Amariglo N, Rechavi G, Li J, Ravid R, Roggendorf W, Riederer P, Youdim MB (2004) Gene expression profiling of parkinsonian substantia nigra pars compacta alterations in ubiquitin-proteasome, heat shock protein, iron and oxidative stress regulated proteins, cell adhesion/cellular matrix and vesicle trafficking genes. J Neural Transm 111:1543–1573
Patel S, Singh K, Singh S, Singh MP (2008) Gene expression profiles of mouse striatum in control and maneb + paraquat-induced Parkinson’s disease phenotype: validation of differentially expressed energy metabolizing transcripts. Mol Biotechnol 40:59–68
Duke DC, Moran LB, Kalaitzakis ME, Deprez M, Dexter DT, Pearce RK, Graeber MB (2006) Transcriptome analysis reveals link between proteasomal and mitochondrial pathways in Parkinson’s disease. Neurogenetics 7:139–148
Miller RM, Kiser GL, Kaysser-Kranich TM (2006) Robust dysregulation of gene expression in substantia nigra and striatum in Parkinson’s disease. Neurobiol Dis 21:305–313
Chin MH, Qian WJ, Wang H, Petyuk VA, Bloom JS, Sforza DM, Laćan G, Liu D, Khan AH, Cantor RM, Bigelow DJ, Melega WP, Camp DG 2nd, Smith RD, Smith DJ (2008) Mitochondrial dysfunction, oxidative stress, and apoptosis revealed by proteomic and transcriptomic analyses of the striata in two mouse models of Parkinson’s disease. J Proteome Res 7:666–677
Cadet JL, Brannock C, Krasnova IN, Ladenheim B, McCoy MT, Chou J, Lehrmann E, Wood WH, Becker KG, Wang Y (2010) Methamphetamine-induced dopamine-independent alterations in striatal gene expression in the 6-hydroxydopamine hemiparkinsonian rats. PLoS One 5:e15643
Pickrell AM, Fukui H, Wang X, Pinto M, Moraes CT (2011) The striatum is highly susceptible to mitochondrial oxidative phosphorylation dysfunctions. J Neurosci 631:9895–9904
Grünblatt E (2012) Parkinson’s disease: molecular risk factors. Parkinsonism Relat Disord 18(Suppl 1):S45–S48
Wernicke C, Hellmann J, Zieba B, Kuter K, Ossowska K, Frenzel M, Dencher NA, Rommelspacher H (2010) 9-Methyl-beta-carboline has restorative effects in an animal model of Parkinson’s disease. Pharmacol Rep 62:35–53
Pattarini R, Rong Y, Qu C, Morgan JI (2008) Distinct mechanisms of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine resistance revealed by transcriptome mapping in mouse striatum. Neuroscience 155:1174–1194
Chung CY, Seo H, Sonntag KC, Brooks A, Lin L, Isacson O (2005) Cell type-specific gene expression of midbrain dopaminergic neurons reveals molecules involved in their vulnerability and protection. Hum Mol Genet 14:1709–1725
Mandel S, Grunblatt E, Maor G, Youdim MB (2002) Early and late gene changes in MPTP mice model of Parkinson’s disease employing cDNA microarray. Neurochem Res 27:1231–1243
Grunblatt E, Mandel S, Maor G, Youdim MB (2001) Gene expression analysis in N-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine mice model of Parkinson’s disease using cDNA microarray: effect of R-apomorphine. J Neurochem 78:1–12
Tomita H, Vawter MP, Walsh DM, Evans SJ, Choudary PV, Li J, Overman KM, Atz ME, Myers RM, Jones EG, Watson SJ, Akil H, Bunney WE Jr (2004) Effect of agonal and postmortem factors on gene expression profile: quality control in microarray analyses of postmortem human brain. Biol Psychiatry 55:346–352
Mischak H, Apweiler R, Banks RE, Conaway M, Coon J, Dominiczak A, Ehrich JH, Fliser D, Girolami M, Hermjakob H, Hochstrasser D, Jankowski J, Julian BA, Kolch W, Massy ZA, Neusuess C, Novak J, Peter K, Rossing K, Schanstra J, Semmes OJ, Theodorescu D, Thongboonkerd V, Weissinger EM, Van Eyk JE, Yamamoto T (2007) Clinical proteomics: a need to define the field and to begin to set adequate standards. Proteomics Clin Appl 1:148–156
Zhang J, Keene CD, Pan C, Montine KS, Montine TJ (2008) Proteomics of human neurodegenerative diseases. J Neuropathol Exp Neurol 67:923–932
Pienaar IS, Daniels WM, Gotz J (2008) Neuroproteomics as a promising tool in Parkinson’s disease research. J Neural Transm 115:1413–1430
Butler GS, Overall CM (2009) Proteomic identification of multitasking proteins in unexpected locations complicates drug targeting. Nat Rev Drug Discov 8:935–948
Farley AR, Link AJ (2009) Identification and quantification of protein posttranslational modifications. Methods Enzymol 463:725–763
Hwang H, Zhang J, Chung KA, Leverenz JB, Zabetian CP, Peskind ER, Jankovic J, Su Z, Hancock AM, Pan C, Montine TJ, Pan S, Nutt J, Albin R, Gearing M, Beyer RP, Shi M, Zhang J (2010) Glycoproteomics in neurodegenerative diseases. Mass Spectrom Rev 29:79–125
Zhang J, Goodlett DR (2004) Proteomic approach to studying Parkinson’s disease. Mol Neurobiol 29:271–288
Robinson PA (2010) Understanding the molecular basis of Parkinson’s disease, identification of biomarkers and routes to therapy. Expert Rev Proteomics 7:565–578
Liu B, Shi Q, Ma S, Feng N, Li J, Wang L, Wang X (2008) Striatal 19S Rpt6 deficit is related to alpha-synuclein accumulation in MPTP-treated mice. Biochem Biophys Res Commun 376:277–282
Zhang X, Zhou JY, Chin MH, Schepmoes AA, Petyuk VA, Weitz KK, Petritis BO, Monroe ME, Camp DG, Wood SA, Melega WP, Bigelow DJ, Smith DJ, Qian WJ, Smith RD (2010) Region-specific protein abundance changes in the brain of MPTP-induced Parkinson’s disease mouse model. J Proteome Res 9:1496–1509
Jin J, Hulette C, Wang Y (2006) Proteomic identification of a stress protein, mortalin/mthsp70/GRP75: relevance to Parkinson disease. Mol Cell Proteomics 5:1193–1204
Park B, Yang J, Yun N, Choe KM, Jin BK, Oh YJ (2010) Proteomic analysis of expression and protein interactions in a 6-hydroxydopamine-induced rat brain lesion model. Neurochem Int 57:16–32
Lessner G, Schmitt O, Haas SJ, Mikkat S, Kreutzer M, Wree A, Glocker MO (2010) Differential proteome of the striatum from hemiparkinsonian rats displays vivid structural remodeling processes. J Proteome Res 9:4671–4687
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. Brain Res Mol Brain Res 134:119–138
Shi M, Caudle WM, Zhang J (2009) Biomarker discovery in neurodegenerative diseases: a proteomic approach. Neurobiol Dis 35:157–164
Goldknopf IL (2008) Blood-based proteomics for personalized medicine: examples from neurodegenerative disease. Expert Rev Proteomics 5:1–8
Sinha A, Srivastava N, Singh S, Singh AK, Bhushan S, Shukla R, Singh MP (2009) Identification of differentially displayed proteins in cerebrospinal fluid of Parkinson’s disease patients: a proteomic approach. Clin Chim Acta 400:14–20
van Dijk KD, Teunissen CE, Drukarch B, Jimenez CR, Groenewegen HJ, Berendse HW, van de Berg WD (2010) Diagnostic cerebrospinal fluid biomarkers for Parkinson’s disease: a pathogenetically based approach. Neurobiol Dis 39:229–241
Tribl F, Marcus K, Bringmann G, Meyer HE, Gerlach M, Riederer P (2006) Proteomics of the human brain: sub-proteomes might hold the key to handle brain complexity. J Neural Transm 113:1041–1054
Sinha A, Patel S, Singh MP, Shukla R (2007) Blood proteome profiling in case controls and Parkinson’s disease patients in Indian population. Clin Chim Acta 380:232–234
Chen HM, Lin CY, Wang V (2011) Amyloid P component as a plasma marker for Parkinson’s disease identified by a proteomic approach. Clin Biochem 44:377–385
Waragai M, Wei J, Fujita M, Nakai M, Ho GJ, Masliah E, Akatsu H, Yamada T, Hashimoto M (2006) Increased level of DJ-1 in the cerebrospinal fluids of sporadic Parkinson’s disease. Biochem Biophys Res Commun 345:967–972
Muntané G, Dalfó E, Martinez A, Ferrer I (2008) Phosphorylation of tau and alpha-synuclein in synaptic-enriched fractions of the frontal cortex in Alzheimer’s disease, and in Parkinson’s disease and related alpha-synucleinopathies. Neuroscience 152:913–923
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 279:13256–13264
Salahpour A, Medvedev IO, Beaulieu JM, Gainetdinov RR, Caron MG (2007) Local knockdown of genes in the brain using small interfering RNA: a phenotypic comparison with knockout animals. Biol Psychiatry 61:65–69
Ko HS, Bailey R, Smith WW, Liu Z, Shin JH, Lee YI, Zhang YJ, Jiang H, Ross CA, Moore DJ, Patterson C, Petrucelli L, Dawson TM, Dawson VL (2009) CHIP regulates leucine-rich repeat kinase-2 ubiquitination, degradation, and toxicity. Proc Natl Acad Sci U S A 106:2897–2902
Ko HS, Lee Y, Shin JH, Karuppagounder SS, Gadad BS, Koleske AJ, Pletnikova O, Troncoso JC, Dawson VL, Dawson TM (2010) Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin’s ubiquitination and protective function. Proc Natl Acad Sci U S A 107:16691–16696
Cai J, Donaldson A, Yang M, German MS, Enikolopov G, Iacovitti L (2009) The role of Lmx1a in the differentiation of human embryonic stem cells into midbrain dopamine neurons in culture and after transplantation into a Parkinson’s disease model. Stem Cells 27:220–229
Kim J, Inoue K, Ishii J, Vanti WB, Voronov SV, Murchison E, Hannon G, Abeliovich A (2007) A MicroRNA feedback circuit in midbrain dopamine neurons. Science 317:1220–1224
Nelson PT, Wang WX, Rajeev BW (2008) MicroRNAs (miRNAs) in neurodegenerative diseases. Brain Pathol 18:130–138
Hebert SS, De Strooper B (2009) Alterations of the microRNA network cause neurodegenerative disease. Trends Neurosci 32:199–206
Miñones-Moyano E, Porta S, Escaramís G, Rabionet R, Iraola S, Kagerbauer B, Espinosa-Parrilla Y, Ferrer I, Estivill X, Martí E (2011) MicroRNA profiling of Parkinson’s disease brains identifies early downregulation of miR-34b/c which modulate mitochondrial function. Hum Mol Genet 20:3067–3078
Greco SJ, Rameshwar P (2007) MicroRNAs regulate synthesis of the neurotransmitter substance P in human mesenchymal stem cell-derived neuronal cells. Proc Natl Acad Sci U S A 104:15484–15489
Ziviani E, Tao RN, Whitworth AJ (2010) Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin. Proc Natl Acad Sci USA 107:5018–5023
Geisler S, Holmstrom KM, Skuja D, Fiesel FC, Rothfuss OC, Kahle PJ, Springer W (2010) PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol 12:119–131
Scherzer CR, Grass JA, Liao Z, Pepivani I, Zheng B, Eklund AC, Ney PA, Ng J, McGoldrick M, Mollenhauer B, Bresnick EH, Schlossmacher MG (2008) GATA transcription factors directly regulate the Parkinson’s disease-linked gene alpha-synuclein. Proc Natl Acad Sci U S A 105:10907–10912
Doxakis E (2010) Post-transcriptional regulation of alpha-synuclein expression by mir-7 and mir-153. J Biol Chem 285:12726–12734
Wang G, van der Walt JM, Mayhew G, Li YJ, Zuchner S, Scott WK, Martin ER, Vance JM (2008) Variation in the miRNA-433 binding site of FGF20 confers risk for Parkinson disease by overexpression of alpha-synuclein. Am J Hum Genet 82:283–289
Toda T, Momose Y, Murata M, Tamiya G, Yamamoto M, Hattori N, Inoko H (2003) Toward identification of susceptibility genes for sporadic Parkinson’s disease. J Neurol 250:III40–III43
Galvin JE (2004) Neurodegenerative diseases: pathology and the advantage of single-cell profiling. Neurochem Res 29:1041–1051
Scherzer CR, Eklund AC, Morse LJ, Liao Z, Locascio JJ, Fefer D, Schwarzschild MA, Schlossmacher MG, Hauser MA, Vance JM, Sudarsky LR, Standaert DG, Growdon JH, Jensen RV, Gullans SR (2007) Molecular markers of early Parkinson’s disease based on gene expression in blood. Proc Natl Acad Sci U S A 104:955–960
Sinha A, Singh C, Parmar D, Singh MP (2007) Proteomics in clinical interventions: achievements and limitations in biomarker development. Life Sci 2080:1345–1354
Patel S, Sinha A, Singh MP (2007) Identification of differentially expressed proteins in striatum of maneb- and paraquat-induced Parkinson’s disease phenotype in mouse. Neurotoxicol Teratol 29:578–585
Gerlach M, Riederer P (1996) Animal models of Parkinson’s disease: an empirical comparison with the phenomenology of the disease in man. J Neural Transm 103:987–1041
Laterra J, Keep R, Betz LA, Goldstein GW (1999) Blood–brain barrier. In: Siegel GJ, Agranoff BW, Albers RW et al (eds) Basic neurochemistry: molecular, cellular and medical aspects, 6th edn. Lippincott-Raven, Philadelphia
Robbins M, Judge A, Liang L, McClintock K, Yaworski E, MacLachlan I (2007) 2′-O-methyl-modified RNAs act as TLR7 antagonists. Mol Ther 15:1663–1669
Ma Z, Li J, He F, Wilson A, Pitt B, Li S (2005) Cationic lipids enhance siRNA-mediated interferon response in mice. Biochem Biophys Res Commun 330:755–759
Hornung V, Guenthner-Biller M, Bourquin C, Ablasser A, Schlee M, Uematsu S, Noronha A, Manoharan M, Akira S, de Fougerolles A, Endres S, Hartmann G (2005) Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat Med 11:263–270
Acknowledgments
We sincerely thank the Council of Scientific and Industrial Research (CSIR), New Delhi, India/University Grants Commission, New Delhi, India for providing research fellowships to Sharawan Yadav, Sonal Agrawal, Garima Srivastava, Anand Kumar Singh, and Anubhuti Dixit. The CSIR-IITR communication number of the article is 3012.
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Authors Sharawan Yadav and Anubhuti Dixit contributed equally to this work.
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Yadav, S., Dixit, A., Agrawal, S. et al. Rodent Models and Contemporary Molecular Techniques: Notable Feats yet Incomplete Explanations of Parkinson’s Disease Pathogenesis. Mol Neurobiol 46, 495–512 (2012). https://doi.org/10.1007/s12035-012-8291-8
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DOI: https://doi.org/10.1007/s12035-012-8291-8