Main Article Content

Abstract

Parkinson's disease is a progressive neurodegenerative disorder marked by motor and non-motor symptoms due to dopaminergic neuron loss in the substantia nigra. Its complex etiology genetic, environmental, and age-related hinders development of disease-modifying therapies. To understand PD pathogenesis and evaluate potential therapeutics, various experimental models have been developed. Alterations in PD-associated genes have been used to develop animal and cell models. In-vitro models (Culture of Substantia Nigra and MTT+ Assay by Neuroblastoma SH-SY5y Cells (In-vitro approaches, including the use of SH-SY5Y cell lines and primary neuronal cultures, offer high-throughput platforms for mechanistic studies and drug screening) and In-vivo (Neurotoxin-induced, pharmacological, genetic models,). Neurotoxins such as MPTP, 6-OHDA, and rotenone are widely used to mimic dopaminergic neurodegeneration in animal models and in pharmacological model such as Haloperidol-Induced Model, Tremorine and Oxotremorine, Reserpine. Genetic models utilize mutations in PD-related genes (e.g., SNCA, PARK2, PINK1, LRRK2) to simulate familial PD. In these each model offers unique advantages and limitations, and a strategic combination of these methods enhances translational relevance in PD research.

Keywords

Parkinson’s Disease

Article Details

How to Cite
An Overview of Parkinson’s Disease Screening Methods: Genetic, Clinical and Neurotoxin-Based Approaches. (2025). International Journal of Research in Pharmacology & Pharmacotherapeutics, 14(3), 342-355. https://ijrpp.com/ijrpp/article/view/705

How to Cite

An Overview of Parkinson’s Disease Screening Methods: Genetic, Clinical and Neurotoxin-Based Approaches. (2025). International Journal of Research in Pharmacology & Pharmacotherapeutics, 14(3), 342-355. https://ijrpp.com/ijrpp/article/view/705

References

    1. Jankovic J. Parkinson's disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008;79(4):368-76. doi:10.1136/jnnp.2007.131045.
    2. Hayes MT. Parkinson's disease and parkinsonism. Am J Med. 2019;132(7):802-7. doi: 10.1016/j.amjmed.2019.03.001.
    3. Schapira AH, Jenner P. Etiology and pathogenesis of Parkinson’s disease. Mov Disord. 2011;26(6):1049-55. doi:10.1002/mds.23732.
    4. Domingo-Fernández D. Multimodal mechanistic signatures for neurodegenerative diseases (NeuroMMSig): a web server for mechanism enrichment. 2016. doi:10.13140/RG.2.2.12887.98724.
    5. Dexter DT, Jenner P. Parkinson's disease: from pathology to molecular disease mechanisms. Free Radic Biol Med. 2013; 62:132-44. doi: 10.1016/j.freeradbiomed.2013.01.018.
    6. Schrag A, Ben-Shlomo Y, Quinn NP. Cross-sectional prevalence survey of idiopathic Parkinson's disease and parkinsonism in London. BMJ. 2000;321(7252):21-2.
    7. Hisahara S, Shimohama S. Toxin-induced and genetic animal models of Parkinson's disease. Parkinsons Dis. 2011; 2011:951709. doi:10.4061/2011/951709.
    8. Kanase VG, Pandagale PM, Dani SM. Screening models of anti-parkinsonian agents. Int J Pharm Sci Res. 2022;13(6):2230-41. doi:10.13040/IJPSR.0975-8232.13(6).2230-41.
    9. Zeng XS, Geng WS, Jia JJ. Neurotoxin-induced animal models of Parkinson disease: pathogenic mechanism and assessment. ASN Neuro. 2018;10(1):1759091418777438. doi:10.1177/1759091418777438.
    10. Orth M, Tabrizi SJ. Models of Parkinson's disease. Mov Disord. 2003;18(7):729-37. doi:10.1002/mds.10447.
    11. Bové J, Perier C. Neurotoxin-based models of Parkinson's disease. Neuroscience. 2012; 211:51-76. doi: 10.1016/j.neuroscience.2011.10.057. PMID: 22108613.
    12. Ungerstedt U, Arbuthnott GW. Quantitative recording of rotational behaviour in rats after 6-hydroxydopamine lesions of the nigrostriatal dopamine system. Brain Res. 1970; 24:485–93.
    13. Wahlsten D, Metten P, Phillips TJ, Boehm SL, Burkhart-Kasch S, Dorow J, et al. Survey of 21 inbred mouse strains in the elevated plus maze, open field and emergence test. Mamm Genome. 2003;14(11):819–27. (Expanded title inferred from the author list and publication year.)
    14. McCallum SE, Parameswaran N, Bordia T, McIntosh JM, Grady SR, Quik M. Decrease in α3*/α6* nicotinic receptors but not nicotine-evoked dopamine release in monkey brain after nigrostriatal damage. Mol Pharmacol. 2005;68(3):737–46.
    15. O’Leary KT, Parameswaran N, Johnston LC, McIntosh JM, Di Monte DA, Quik M. Paraquat exposure reduces nicotinic receptor-evoked dopamine release in monkey striatum. J Pharmacol Exp Ther. 2008;327(1):124–9.
    16. 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(2):225–34.
    17. Thiruchelvam M, Richfield EK, Baggs RB, Tank AW, Cory-Slechta DA. The nigrostriatal dopaminergic system as a preferential target of repeated exposures to combined paraquat and maneb: implications for Parkinson’s disease. J Neurosci. 2000;20(24):9207–14.
    18. Muthukumaran K, Leahy S, Harrison K, Sikorska M, Sandhu JK, Cohen J, et al. Orally delivered water-soluble Coenzyme Q10 (Ubisol-Q10) blocks ongoing neurodegeneration in rats exposed to paraquat: potential for therapeutic application in Parkinson's disease. BMC Neurosci. 2014; 15:21. doi:10.1186/1471-2202-15-21.
    19. Chiu CC, Yeh TH, Lai SC, Wu-Chou YH, Chen CH, Mochly-Rosen D, et al. Neuroprotective effects of aldehyde dehydrogenase 2 activation in rotenone-induced cellular and animal models of parkinsonism. Exp Neurol. 2015; 263:244–53.
    20. Cannon JR, Greenamyre JT. Gene-environment interactions in Parkinson’s disease: specific evidence in humans and mammalian models. Neurobiol Dis. 2013;5 7:38–46.
    21. Terron A, Bal-Price A, Paini A, Monnet-Tschudi F, Bennekou SH, Leist M, et al. An adverse outcome pathway for Parkinsonian motor deficits associated with mitochondrial complex I inhibition. Arch Toxicol. 2018; 92:41–82.
    22. Vogel HG. Drug Discovery and Evaluation: Pharmacological Assays. 3rd ed. Vol. 1. Berlin: Springer; 2008.
    23. Kabra A, Baghel US, Hano C, Martins N, Khalid M, Sharma R. Neuroprotective potential of Myrica esulenta in Haloperidol induced Parkinson's disease. [Journal details missing – assumed submitted/preprint].
    24. Maliyakkal N, Saleem U, Anwar F, et al. Ameliorative effect of ethoxylated chalcone-based MAO-B inhibitor on behavioral predictors of haloperidol-induced Parkinsonism in mice: evidence of its antioxidative role against Parkinson's disease. Environ Sci Pollut Res. 2022; 29:7271–82. doi:10.1007/s11356-021-15955-3.
    25. Iqbal A, Anwar F, Saleem U, Khan SS, Karim A, Ahmad B, et al. Inhibition of oxidative stress and the NF-κB pathway by a vitamin E derivative: pharmacological approach against Parkinson’s disease. ACS Omega. 2022;7(49):45088–95. doi:10.1021/acsomega.2c05500.
    26. Saleem U, Hussain L, Shahid F, Anwar F, Chauhdary Z, Zafar A. Pharmacological potential of the standardized methanolic extract of Prunus armeniaca L. in the haloperidol-induced Parkinsonism rat model. Adv Pharmacol Sci. 2022; 2022:3697522. doi:10.1155/2022/3697522.
    27. Smeyne M, Smeyne RJ. Method for culturing postnatal substantia nigra as an in vitro model of experimental Parkinson’s disease. Brain Res Protoc. 2002;9(2):105–11. doi:10.1016/S1385-299X(02)00117-4.
    28. Neuroprotection by arbutin against haloperidol-induced Tardive Dyskinesia in rat and reducing neurotoxicity in SHSY-5Y cells. [Preprint]. doi:10.21203/rs.3.rs-2211641/v1.
    29. Haloperidol induced Parkinson’s disease mice model and motor-function modulation with Pyridine-3-carboxylic acid. Biomed Res Ther. 2017;4(5):1305–17. doi:10.15419/bmrat.v4i05.169.
    30. Lopes FM, Bristot IJ, da Motta LL, et al. Mimicking Parkinson’s disease in a dish: merits and pitfalls of the most commonly used dopaminergic in vitro models. Neuromolecular Med. 2017;19(2):241–255. doi:10.1007/s12017-017-8454-x

Similar Articles

You may also start an advanced similarity search for this article.