An Overview of Animal Models and Symptomatic Treatment of Parkinson’s disease
DOI:
https://doi.org/10.22270/ajprd.v11i3.1271Keywords:
Parkinson disease, Models, Toxicant, Genetic, Treatment.Abstract
The broad theory indicate that neurological ailment is caused by intricate interactions between environmental and genetic factors is supported using animal models to better understand the the cause and pathogenesis of Parkinson's disease (PD), as well as its cellular and molecular mechanisms. The more recent models use genetic manipulations that either introduce mutations similar to those found in familial cases of PD (a-synuclein, DJ-1, PINK1, Parkin, etc.) or selectively disrupt nigrostriatal neurons (MitoPark, Pitx3, Nurr1, etc.). "Classic" models are based on neurotoxins that specifically target catecholaminergic neurons. All of these together each model has its own benefits and drawbacks. The use of medication, deep brain stimulation, and physical therapy has been optimised for the symptomatic treatment of the motor symptoms of Parkinson disease (PD). L-dopa, several dopamine agonists, inhibitors of MAO-B and catechol-o-methyltransferase (COMT), and amantadine are among the pharmacotherapies available.
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References
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8. Gubellini P, Picconi B, Di FM, Calabresi P. Downstream mechanisms triggered by mitochondrial dysfunction in the basal ganglia: from experimental models to neurodegenerative diseases. Biochim Biophys Acta 2010; 1802(1):151–61.
9. Dauer W, Przedborski S. Parkinson’s disease: mechanisms and models. Neuron 2003; 39(6):889–909.
10. Schapira AH, Cooper JM, Dexter D, Clark JB, Jenner P, Marsden CD. Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem 1990; 54(3):823–7.
11. Ungerstedt U. 6-Hydroxy-dopamine induced degeneration of central monoamine neurons. Eur J Pharmacol 1968; 5(1):107–10.
12. Porter CC, Totaro JA, Stone CA. Effect of 6- hydroxydopamine and some other compounds on the concentration of norepinephrine in the hearts of mice. J Pharmacol Exp Ther1963; 140:308–16.
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14. ¬Faull RL, Laverty R,changes in dopamine level in striatum following lesion in substantia nigra Exp neurol 1969:23:332-340.
15. Lee CS, Sauer H, Bjorklund A. Dopaminergic neuronal degeneration and motor impairments following axon terminal lesion by instrastriatal 6-hydroxydopamine in the rat. Neuroscience 1996; 72:641–53.
16. Alves da Costa C, Dunys J, Brau F, Wilk S, Cappai R, Checler F. 6-Hydroxydopamine but not 1-methyl-4-phenylpyridinium abolishes alpha-synuclein anti-apoptotic phenotype by inhibiting its proteasomal degradation and by promoting its aggregation. J Biol Chem 2006; 281:9824–31.
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21. Chiueh CC, Markey SP, Burns RS, Johannessen JN, Jacobowitz DM, Kopin IJ. Neurochemical and behavioral effects of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) in rat, guinea pig, and monkey. Psychopharmacol Bull 1984; 20:548–53.
22. Smeyne RJ, Jackson-Lewis V. The MPTP model of Parkinson’s disease. Brain Res Mol Brain Res 2005; 134(1):57–66.
23. Ranjita betarbet,ToddB,Sherer et al animal models of Parkinson disease bioassay 24:308-318 2002 wiley periodicals .inc DOI 10:1002/bies .10067.
24. Berry C, La Vecchia C, Nicotera P. Paraquat and Parkinson’s disease. Cell Death Differ 2010; 17:1115–25.
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26. Ossowska K, Wardas J, Smialowska M, Kuter K, Lenda T, Wieronska JM, et al. A slowly developing dysfunction of dopaminergic nigrostriatal neurons induced by long-term paraquat administration in rats: an animal model of preclinical stages of Parkinson’s disease? Eur J Neurosci 2005; 22(6):1294–304.
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28. Day BJ, Patel M, Calavetta L, Chang LY, Stamler JS. A mechanism of paraquat toxicity involving nitric oxide synthase. Proc Natl Acad Sci U S A 1999; 96(22):12760–5.
29. Brooks AI, Chadwick CA, Gelbard HA, Cory-Slechta DA, Federoff HJ. Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss. Brain Res 1999; 823(1–2):1–10.
30. Thiruchelvam M, Brockel BJ, Richfield EK, Baggs RB, Cory-Slechta DA. Potentiated and preferential effects of combined paraquat and maneb on nigrostriatal dopamine systems: environmental risk factors for Parkinson’s disease? Brain Res 2000; 873:225–34.
31. Manning-Bog AB, McCormack AL, Li J, Uversky VN, Fink AL, Di Monte DA. The herbicide paraquat causes upregulation and aggregation of alpha-synuclein in mice: paraquat and alpha-synuclein. J Biol Chem 2002; 277(3):1641–4.
32. Takahashi RN, Rogerio R, Zanin M. Maneb enhances MPTP neurotoxicity in mice. Res Commun Chem Pathol Pharmacol 1989; 66(1):167–70.
33. Miller GW. Paraquat: the red herring of Parkinson’s disease research. Toxicol Sci 2007; 100(1):1–2.
34. Greenamyre JT, Betarbet R, Sherer TB. The rotenone model of Parkinson’s disease: genes, environment and mitochondria. Parkinsonism RelatDisord 2003; 9(Suppl. 2):S59–64.
35. Greenamyre JT, Cannon JR, Drolet R, Mastroberardino PG. Lessons from the rotenone model of Parkinson’s disease. Trends Pharmacol Sci 2010; 31(4):141–2.
36. Degli Esposti M inhibitor of NABH ubiquinone reductase overview biochimbiosphy acta 1999:1364:222:235.
37. Verstraeten A, Theuns J, Van BC. Progress in unraveling the genetic etiology of Parkinson disease in a genomic era. Trends Genet 2015; 31(3):140–9.
38. M.H. Polymeropoulos, C. Lavedan, E. Leroy, S.E. Ide, A. Dehejia, A. Dutra, B. Pike, H. Root, J. Rubenstein, R. Boyer, E.S. Stenroos, S. Chandrasekharappa, A. Athanassiadou, T. Papapetropoulos, W.G. Johnson, A.M. Lazzarini, R.C. Duvoisin, G. Di Iorio, L.I. Golbe, R.L. Nussbaum, Mutation in the alphasynuclein gene identified in families with Parkinson's disease, Science 276 (1997) 2045–2047.
39. T. Kitada, S. Asakawa, N. Hattori, H. Matsumine, Y. Yamamura, S. Minoshima, M. Yokochi, Y. Mizuno, N. Shimizu, Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism, Nature 392 (1998) 605–608.
40. Kitada T, Tong Y, Gautier CA, Shen J. Absence of nigral degeneration in aged parkin/DJ-1/PINK1 triple knockout mice. J Neurochem 2009;1 11(3):696–702.
41. K.-L. Lim, C.-H. Ng Genetic models of Parkinson disease Biochimical et Biophysica Acta 1792 (2009) 604–615.
42. D.D. Murphy, S.M. Rueter, J.Q. Trojanowski, V.M. Lee, Synucleins are developmentally expressed, and alpha-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons, J. Neurosci. 20 (2000) 3214–3220.
43. Verstraeten A, Theuns J, Van BC. Progress in unraveling the genetic etiology of Parkinson disease in a genomic era. Trends Genet 2015; 31(3):140–9.
44. P.Gubellini, P. Kachidian, Animal models of Parkinson’s disease: An updated overview Revue neurologique (2015), http://dx.doi.org/10.1016/j.neurol.2015.07.011.
45. Kah-Leong Lim , Chee-Hoe Ng,Genetic models of Parkinson disease Biochimica et Biophysica Acta 1792 (2009) 604–615.
46. Dawson TM, Dawson VL. The role of parkin in familial and sporadic Parkinson’s disease. Mov Disord 2010; 25(Suppl. 1):S32–9.
47. Lazarou M, Narendra DP, Jin SM, Tekle E, Banerjee S, Youle RJ. PINK1 drives Parkin self-association and HECT-like E3 activity upstream of mitochondrial binding. J Cell Biol 2013; 200(2):163–72.
48. Valente EM, bou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, et al. Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science 2004; 304(5674):1158–60.
49. Oliveras-Salva M, Macchi F, Coessens V, Deleersnijder A, Gerard M, Van der PA, et al. Alpha-synuclein-induced neurodegeneration is exacerbated in PINK1 knockout mice. Neurobiol Aging 2014; 35(11):2625–36.
50. Hedrich K, Djarmati A, Schafer N, Hering R, Wellenbrock C, Weiss PH, et al. DJ-1 (PARK7) mutations are less frequent than Parkin (PARK2) mutations in early-onset Parkinson disease. Neurology 2004; 62(3):389–94.
51. Bonifati, P. Rizzu, M.J. Van Baren, O. Schaap, G.J. Breedveld, E. Krieger, M.C. Dekker, F. Squitieri, P. Ibanez, M. Joosse, J.W. Van Dongen, N. Vanacore, J.C. Van Swieten, A. Brice, G. Meco, C.M. Van Duijn, B.A. Oostra, P. Heutink, Mutations in the DJ-1 gene associated with autosomal recessive early-onset Parkinsonism, Science 299 (2002) 256–259.
52. 53.Pham TT, Giesert F, Rothig A, Floss T, Kallnik M, Weindl K, et al. DJ-1-deficient mice show less TH-positive neurons in the ventral tegmental area and exhibit non-motoric behavioural impairments. Genes Brain Behav 2010; 9(3):305–17.
53. Shobha S. Rao, M.D., Laura A Parkinson’s Disease: Diagnosis and Treatment December 2006; 15 (74), Number 12 www.aafp.org/afp American Family Physician.
54. B. S., & Lang, A. E. Parkinson disease: An update. American Family Physician, 2014; 87(4):267-273 and Connolly.
55. Kristina Terzakis, SN Parkinson disease Volume 34 | Number 6 www.homehealthcarenow.org 2016 Wolters Kluwer Health.
56. J. Michael Ellis a, Matthew J. Fell Current approaches to the treatment of Parkinson’s Diseas Bioorganic & Medicinal Chemistry Letters 2017; 27:4247–425.
57. Hedera et al. Pharmacotherapy of Essential Tremor. Journal of Central Nervous System Disease 2013; 5:43–55 doi: 10.4137/JCNSD.S6561.
58. Shah B (2017) Essential Tremor: A Comprehensive Overview. J Neurol Disord 5: 343. doi:10.4172/2329-6895.1000343.
59. W. Oertel and J. B. Schulz International Society for Neurochemistry, J. Neurochem. (2016) 10.1111/jnc.13750.
2. Poewe, W., Seppi, K., Tanner, C. M., Halliday, G. M., Brundin, P., Volkmann, J., Schrag, A.-E., & Lang, A. E. Parkinson disease. Nature Reviews Disease Primers, 2017; 3(1):1–21. https://doi.org/10.1038/ nrdp.2017.13.
3. Hornykiewicz O. The discovery of dopamine deficiency in the parkinsonian brain. J Neural TransmSuppl 2006; 9.
4. Björklund, A., & Dunnett, S. B. Dopamine neuron systems in the brain: An update. Trends in Neurosciences, 2007; 30(5):194–202. https://doi.org/10.1016/j.tins.2007.03.006.
5. Barré-Sinoussi, F., &Montagutelli, X. Animal models are essential to biological research: Issues and perspectives. Future Science OA, 1(4), FSO63. https://doi.org/10.4155/fso.15.636.Parkinson’s disease. Mov Disord 2011; 26 .
6. Malaiwong, N., Chalorak, P., Jattujan, P., Manohong, P., Niamnont, N., Suphamungmee, W., Sobhon, P., & Meemon, K. Anti Parkinson activity of bioactive substances extracted from Holothurialeucospilota. Biomedicine & Pharmacotherapy 2019; 109:1967–1977. https:// doi.org/10.1016/j.biopha.2018.11.063.
7. Dawson TM, Dawson VL. Molecular pathways of neurodegeneration in Parkinson’s disease. Science 2003; 302(5646):819–22.
8. Gubellini P, Picconi B, Di FM, Calabresi P. Downstream mechanisms triggered by mitochondrial dysfunction in the basal ganglia: from experimental models to neurodegenerative diseases. Biochim Biophys Acta 2010; 1802(1):151–61.
9. Dauer W, Przedborski S. Parkinson’s disease: mechanisms and models. Neuron 2003; 39(6):889–909.
10. Schapira AH, Cooper JM, Dexter D, Clark JB, Jenner P, Marsden CD. Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem 1990; 54(3):823–7.
11. Ungerstedt U. 6-Hydroxy-dopamine induced degeneration of central monoamine neurons. Eur J Pharmacol 1968; 5(1):107–10.
12. Porter CC, Totaro JA, Stone CA. Effect of 6- hydroxydopamine and some other compounds on the concentration of norepinephrine in the hearts of mice. J Pharmacol Exp Ther1963; 140:308–16.
13. Blum D, Torch S, Lambeng N, Nissou M, Benabid AL, Sadoul R, et al. Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson’s disease. Prog Neurobiol 2001; 65(2):135–72.
14. ¬Faull RL, Laverty R,changes in dopamine level in striatum following lesion in substantia nigra Exp neurol 1969:23:332-340.
15. Lee CS, Sauer H, Bjorklund A. Dopaminergic neuronal degeneration and motor impairments following axon terminal lesion by instrastriatal 6-hydroxydopamine in the rat. Neuroscience 1996; 72:641–53.
16. Alves da Costa C, Dunys J, Brau F, Wilk S, Cappai R, Checler F. 6-Hydroxydopamine but not 1-methyl-4-phenylpyridinium abolishes alpha-synuclein anti-apoptotic phenotype by inhibiting its proteasomal degradation and by promoting its aggregation. J Biol Chem 2006; 281:9824–31.
17. Ballard PA, Tetrud JW, Langston JW. Permanent human parkinsonism due to 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP): seven cases. Neurology 1985; 35(7):949–56.
18. Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic Parkinsonism in humans due to a product of meperidineanalog synthesis. Science 1983; 219(4587):979–80.
19. Cui M, Aras R, Christian WV, Rappold PM, Hatwar M, Panza J, et al. The organic cation transporter-3 is a pivotal modulator of neurodegeneration in the nigrostriatal dopaminergic pathway. Proc Natl Acad Sci U S A 2009; 106:8043–8.
20. Hantrayep ,VarastetM, Peschanski M, Riche D, Cesaao P, Wiler JC , Maziere M, stable parkinsonian syndrome and uneven loss of striatal dopamine fibres following chronic MPTP administration in baboons neuroscience 1993:53:179-178.
21. Chiueh CC, Markey SP, Burns RS, Johannessen JN, Jacobowitz DM, Kopin IJ. Neurochemical and behavioral effects of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) in rat, guinea pig, and monkey. Psychopharmacol Bull 1984; 20:548–53.
22. Smeyne RJ, Jackson-Lewis V. The MPTP model of Parkinson’s disease. Brain Res Mol Brain Res 2005; 134(1):57–66.
23. Ranjita betarbet,ToddB,Sherer et al animal models of Parkinson disease bioassay 24:308-318 2002 wiley periodicals .inc DOI 10:1002/bies .10067.
24. Berry C, La Vecchia C, Nicotera P. Paraquat and Parkinson’s disease. Cell Death Differ 2010; 17:1115–25.
25. Brooks AL Chadwick CA GelbardHA, Cloryceshata DA, Fedroff HJ Paraquate elicited neurobehavioral syndrome caused by dopaminergic neuron loss,brain res 1999:823:1-10.
26. Ossowska K, Wardas J, Smialowska M, Kuter K, Lenda T, Wieronska JM, et al. A slowly developing dysfunction of dopaminergic nigrostriatal neurons induced by long-term paraquat administration in rats: an animal model of preclinical stages of Parkinson’s disease? Eur J Neurosci 2005; 22(6):1294–304.
27. Ossowska K, Smialowska M, Kuter K, Wieronska J, Zieba B, Wardas J, et al. Degeneration of dopaminergic mesocortical neurons and activation of compensatory processes induced by a long-term paraquat administration in rats: implications for Parkinson’s disease. Neuroscience 2006; 141(4):2155–65.
28. Day BJ, Patel M, Calavetta L, Chang LY, Stamler JS. A mechanism of paraquat toxicity involving nitric oxide synthase. Proc Natl Acad Sci U S A 1999; 96(22):12760–5.
29. Brooks AI, Chadwick CA, Gelbard HA, Cory-Slechta DA, Federoff HJ. Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss. Brain Res 1999; 823(1–2):1–10.
30. Thiruchelvam M, Brockel BJ, Richfield EK, Baggs RB, Cory-Slechta DA. Potentiated and preferential effects of combined paraquat and maneb on nigrostriatal dopamine systems: environmental risk factors for Parkinson’s disease? Brain Res 2000; 873:225–34.
31. Manning-Bog AB, McCormack AL, Li J, Uversky VN, Fink AL, Di Monte DA. The herbicide paraquat causes upregulation and aggregation of alpha-synuclein in mice: paraquat and alpha-synuclein. J Biol Chem 2002; 277(3):1641–4.
32. Takahashi RN, Rogerio R, Zanin M. Maneb enhances MPTP neurotoxicity in mice. Res Commun Chem Pathol Pharmacol 1989; 66(1):167–70.
33. Miller GW. Paraquat: the red herring of Parkinson’s disease research. Toxicol Sci 2007; 100(1):1–2.
34. Greenamyre JT, Betarbet R, Sherer TB. The rotenone model of Parkinson’s disease: genes, environment and mitochondria. Parkinsonism RelatDisord 2003; 9(Suppl. 2):S59–64.
35. Greenamyre JT, Cannon JR, Drolet R, Mastroberardino PG. Lessons from the rotenone model of Parkinson’s disease. Trends Pharmacol Sci 2010; 31(4):141–2.
36. Degli Esposti M inhibitor of NABH ubiquinone reductase overview biochimbiosphy acta 1999:1364:222:235.
37. Verstraeten A, Theuns J, Van BC. Progress in unraveling the genetic etiology of Parkinson disease in a genomic era. Trends Genet 2015; 31(3):140–9.
38. M.H. Polymeropoulos, C. Lavedan, E. Leroy, S.E. Ide, A. Dehejia, A. Dutra, B. Pike, H. Root, J. Rubenstein, R. Boyer, E.S. Stenroos, S. Chandrasekharappa, A. Athanassiadou, T. Papapetropoulos, W.G. Johnson, A.M. Lazzarini, R.C. Duvoisin, G. Di Iorio, L.I. Golbe, R.L. Nussbaum, Mutation in the alphasynuclein gene identified in families with Parkinson's disease, Science 276 (1997) 2045–2047.
39. T. Kitada, S. Asakawa, N. Hattori, H. Matsumine, Y. Yamamura, S. Minoshima, M. Yokochi, Y. Mizuno, N. Shimizu, Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism, Nature 392 (1998) 605–608.
40. Kitada T, Tong Y, Gautier CA, Shen J. Absence of nigral degeneration in aged parkin/DJ-1/PINK1 triple knockout mice. J Neurochem 2009;1 11(3):696–702.
41. K.-L. Lim, C.-H. Ng Genetic models of Parkinson disease Biochimical et Biophysica Acta 1792 (2009) 604–615.
42. D.D. Murphy, S.M. Rueter, J.Q. Trojanowski, V.M. Lee, Synucleins are developmentally expressed, and alpha-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons, J. Neurosci. 20 (2000) 3214–3220.
43. Verstraeten A, Theuns J, Van BC. Progress in unraveling the genetic etiology of Parkinson disease in a genomic era. Trends Genet 2015; 31(3):140–9.
44. P.Gubellini, P. Kachidian, Animal models of Parkinson’s disease: An updated overview Revue neurologique (2015), http://dx.doi.org/10.1016/j.neurol.2015.07.011.
45. Kah-Leong Lim , Chee-Hoe Ng,Genetic models of Parkinson disease Biochimica et Biophysica Acta 1792 (2009) 604–615.
46. Dawson TM, Dawson VL. The role of parkin in familial and sporadic Parkinson’s disease. Mov Disord 2010; 25(Suppl. 1):S32–9.
47. Lazarou M, Narendra DP, Jin SM, Tekle E, Banerjee S, Youle RJ. PINK1 drives Parkin self-association and HECT-like E3 activity upstream of mitochondrial binding. J Cell Biol 2013; 200(2):163–72.
48. Valente EM, bou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, et al. Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science 2004; 304(5674):1158–60.
49. Oliveras-Salva M, Macchi F, Coessens V, Deleersnijder A, Gerard M, Van der PA, et al. Alpha-synuclein-induced neurodegeneration is exacerbated in PINK1 knockout mice. Neurobiol Aging 2014; 35(11):2625–36.
50. Hedrich K, Djarmati A, Schafer N, Hering R, Wellenbrock C, Weiss PH, et al. DJ-1 (PARK7) mutations are less frequent than Parkin (PARK2) mutations in early-onset Parkinson disease. Neurology 2004; 62(3):389–94.
51. Bonifati, P. Rizzu, M.J. Van Baren, O. Schaap, G.J. Breedveld, E. Krieger, M.C. Dekker, F. Squitieri, P. Ibanez, M. Joosse, J.W. Van Dongen, N. Vanacore, J.C. Van Swieten, A. Brice, G. Meco, C.M. Van Duijn, B.A. Oostra, P. Heutink, Mutations in the DJ-1 gene associated with autosomal recessive early-onset Parkinsonism, Science 299 (2002) 256–259.
52. 53.Pham TT, Giesert F, Rothig A, Floss T, Kallnik M, Weindl K, et al. DJ-1-deficient mice show less TH-positive neurons in the ventral tegmental area and exhibit non-motoric behavioural impairments. Genes Brain Behav 2010; 9(3):305–17.
53. Shobha S. Rao, M.D., Laura A Parkinson’s Disease: Diagnosis and Treatment December 2006; 15 (74), Number 12 www.aafp.org/afp American Family Physician.
54. B. S., & Lang, A. E. Parkinson disease: An update. American Family Physician, 2014; 87(4):267-273 and Connolly.
55. Kristina Terzakis, SN Parkinson disease Volume 34 | Number 6 www.homehealthcarenow.org 2016 Wolters Kluwer Health.
56. J. Michael Ellis a, Matthew J. Fell Current approaches to the treatment of Parkinson’s Diseas Bioorganic & Medicinal Chemistry Letters 2017; 27:4247–425.
57. Hedera et al. Pharmacotherapy of Essential Tremor. Journal of Central Nervous System Disease 2013; 5:43–55 doi: 10.4137/JCNSD.S6561.
58. Shah B (2017) Essential Tremor: A Comprehensive Overview. J Neurol Disord 5: 343. doi:10.4172/2329-6895.1000343.
59. W. Oertel and J. B. Schulz International Society for Neurochemistry, J. Neurochem. (2016) 10.1111/jnc.13750.
Published
2023-06-21
How to Cite
Patil, P., Chaware, V., & Redasani, V. (2023). An Overview of Animal Models and Symptomatic Treatment of Parkinson’s disease. Asian Journal of Pharmaceutical Research and Development, 11(3), 132–135. https://doi.org/10.22270/ajprd.v11i3.1271
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