Modern views on etiology and pathogenesis of Parkinson's disease

Authors

  • А.V. Kutsak State Institution: "Zaporizhzhia Medical Academy of Post-Graduate Education Ministry of Health of Ukraine",
  • N. M. Buchakchyiska State Institution: "Zaporizhzhia Medical Academy of Post-Graduate Education Ministry of Health of Ukraine",

DOI:

https://doi.org/10.14739/2310-1210.2016.6.85533

Keywords:

Parkinson Disease, Etiology, Pathogenesis, Risk Factors

Abstract

Aim. To analyze the specialized scientific literature for data generalization concerning current views on etiology and pathogenesis of Parkinson's disease (PD).

PD is a chronic progressive CNS disease, mainly associated with degeneration of brain’s dopamine-producing neurons, motor and non-motor violations and resulting in persistent disability. Although the PD is the most studied disease among all parkinsonism disorders, there is no consensus on its nature until now. The basis of PD pathomorphology and neurological degeneration is a violation of a-synuclein protein with Lewy’s bodies accumulation in the cells. The formation of pathological a-synuclein is connected with features of genotype, environmental agents and internal processes in the body.

The review presents the current data about etiological and pathogenic mechanisms of PD development. Special attention is paid to the role of genetics, the influence of exogenous agents and the basic factors in the pathogenesis of the disease.

Conclusions. A number of questions of PD etiology and pathogenesis are not quite certain for today. Pathogenetic mechanism of degeneration in PD is heterogeneous: mitochondrial dysfunction, oxidative stress, of proteolytic functions violations (ubiquitin-proteasome system). The reasons which start the degenerative process are varied, and can be both external and internal, as well as their interaction also is possible, which determines the probability of PD development.

Sporadic forms of PD pathogenesis are noticeably different from disease with hereditary predisposition. Verification of risk factors if genes predisposing to the disease development are present has a key role for the complex preventive measures formation in patients with a predisposition to the disease. Despite the fact that genetics has the primary importance in the process initiation for persons with a family history, varied clinical scenario of PD with the presence of identical genetic mutations demonstrates the importance of external factors and their populational specificity. Their identification will provide the basis for the effective preventive and predictive capabilities development. Further study of the role of inflammation, excitotoxicity and oxidative stress in the PD pathogenesis could probably provide an opportunity to change symptomatic therapy of the disease into pathogenetic in the future.

References

Wirdefeldt, K., Adami, H. O., Cole, P., Trichopoulos, D., & Mandel, J. (2011) Epidemiology and etiology of Parkinson’s disease: a review of the evidence. Eur. J. Epidemiol, 26(1), 1–58. doi: 10.1007/s10654-011-9581-6.

Antonini, A., Vitale, C., Barone, P., Cilia, R., Righini, A., Bonuccelli, U., et al. (2012) The relationship between cerebral vascular disease and parkinsonism: the VADO study. Parkinsonism and Related Disorders. 18(6), 775–780. doi: 10.1016/j.parkreldis.2012.03.017.

Lesage, S., & Brice, А. (2009) Parkinson’s disease: from monogenic forms to genetic susceptibility factors. Human Molecular Genetics, 18(R1), 48–59. doi: 10.1093/hmg/ddp012.

Prusiner, S. B. (2001) Shattuck lecture – neurodegenerative disease and prions. N Engl J Med., 344, 1516–1526. doi: 10.1056/NEJM200105173442006.

Brighina, L., Frigerio, R., Schneider, N. K., Lesnick, T. G., de Andrade, M., Cunningham, J. M., et al. (2008) Alpha-synuclein, pesticides, and Parkinson disease: a casecontrol study. Neurology, 70(16), 1461–1469. doi: 10.1212/01.wnl.0000304049.31377.f2.

Lin, M. K., & Farrer, M. J. (2014) Genetics and genomics of Parkinson’s disease. Genome Med, 6(6), 48. doi: 10.1186/gm566.

Schutz, J. B., Lindenau, J., Seyfried, J., & Dichgans, J. (2000) Glutatione, oxidative stress and neurodegeneration. Eur J Biochem, 267, 4904–4911. doi: 10.1046/j.1432-1327.2000.01595.x.

Ilarioshkin, S. N. (2011) Obzor materialov 15-go Mezhdunarodnogo kongressa po bolezni Parkinsona [Review Proceedings of the 15th International Congress of Parkinson's Disease]. Toronto (Kanada).

Di Monte, D. A. (2003) The environment and Parkinson’s disease: is thenigrostriatal system preferentially targeted by neurotoxins? Lancet Neurol, 2(9), 531–8. doi: http://dx.doi.org/10.1016/S1474-4422(03)00501-5.

Punia, S., Das, M., Behari, M., Dihana, M., Govindappa, S. T., Muthane, U., et al. (2011) Leads from xenobiotic metabolism genes for Parkinson’s disease among north Indians. Pharmacogenet. Genomics. 21(12), 790–797. doi: 10.1097/FPC.0b013e32834bcd74.

Defebvre, L. (2010) Parkinson’s disease: Role of genetic and environment factors. Involvement in everyday clinical practice. Rev. Neurol. (Paris), 166(10), 764–9. doi: 10.1016/j.neurol.2010.07.014.

Fang, G., Wirdefeldt, K., Jacks, A., Kamel, F., Ye, W., & Chen, H. (2012) CNS infections, sepsis and risk of Parkinson’s disease. Int. J. Epidemiol, 41(4), 1042–9.

doi: 10.1093/ije/dys052.

Dutta, G., Zhang, P., & Liu, B. (2008) The lipopolysaccharide Parkinson’s disease animal model: mechanistic studies and drug discovery. Fundam. Clin. Pharmacol, 22(5), 453–64. doi: 10.1111/j.1472-8206.2008.00616.x.

Takahashi, M., Yamada, M., Yamada, T., Nakajima, K., Yamamoto, T., & Okada, H. (1995) The substantia nigra is a major target for neurovirulent infl uenza A virus. J. Exp. Med., 181(6), 2161–9.

Jang, H., Boltz, D., Sturm-Ramirez, K., Shepherd, K. R., Jiao, Y., Webster, R., & Smeyne, R. J. (2009) Highly pathogenic H5N1 infl uenza virus can enter the central nervous system and induce neuroinfl ammation and neurodegeneration. Proc. Natl. Acad. Sci. USA., 106(33), 14063–8. doi: 10.1073/pnas.0900096106.

Mori, I., Nishiyama, Y., Yokochi, T., & Kimura, Y. (2005) Olfactory transmission of neurotropic viruses. J. Neurovirl, 11(2), 129–37. doi: 10.1080/13550280590922793.

Olanow, C. W., & McNaught, K. (2011) Parkinson’s disease, proteins, and prions: milestones. Mov. Disord., 26(6), 1056–71. doi: 10.1002/mds.23767.

Lerner, A., & Bagic, A. (2008) Olfactory patogenesis of idiopatic Parkinson. Mov Disod. 23(8), 1076–1084. doi: 10.1002/mds.22066.

Braak, H., Ghebremedhin, E., Rüb, U., Bratzke, H., & Del Tredici, K. (2004) Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res., 318(1), 121–34. doi: 10.1007/s00441-004-0956-9.

Goldstein, D. S, Holmes, C., Li, S. T., Bruce, S., Metman, L. V., & Cannon, R. O. (2000) Cardiac sympathetic denervation in Parkinson disease. Ann. Intern. Med., 133(5), 338–47.

Braak, H., de Vos, R. A., Bohl, J., & Del Tredici, K. (2006) Gastric alpha-synuclein immunoreactive inclusions in Meissner’s and Aurbach’s plexuses in cases staged for Parkinson’s disease-related brain pathology. Neurosci. Lett, 396(1), 67–72. doi: 10.1016/j.neulet.2005.11.012.

Slobodin, T. N. (2011) Sovremennyie predstavleniya o patogeneze bolezni Parkinsona [Current views on the pathogenesis of Parkinson's disease]. J NEjRONEWS, 7(34), 22–27. [in Ukrainian].

Hanisch, U. K., & Kettenmann, H. (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nature Neurosci, 10(11), 1387–1394. doi: 10.1038/nn1997.

Levesque, S., Wilson, B., Gregoria, V., Thorpe, L. B., Dallas, S., Polikov, V. S, et al. (2010) Reactive microgliosis: extracellular micro-calpain and microglia-mediated dopaminergic neurotoxicity. J. Brain, 133, 808–21. doi: 10.1093/brain/awp333.

Zhang, W., Wang, T., Pei, Z., Miller, D. S, Wu, X., Block, M. L, et al. (2005) Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson’s disease. FASEB J., 6, 533–42. doi: 10.1096/fj.04-2751com.

Schulz, J. B., Lindenau, J., Seyfried, J., & Dichgans, J. (2000) Glutathione, oxidative stress and neurodegeneration. Eur. J. Biochem. 267(16), 4904–11. doi: 10.1046/j.1432-1327.2000.01595.x.

Shapira, A.H., & Jenner, P. (2011) Etiology and pathogenesis of Parkinson’s disease. J. Mov. Disordes, 6, 1049–55. doi: 10.1002/mds.23732.

Jenner, P. (2003) Oxidative stress in Parkinson’s disease. J. Annals of neurology, 53(3), 26–38. doi: 10.1002/ana.10483.

Shapira, A. H. V. (2008) Mitochondria in the etiology and pathogenesis of Parkinson's disease. J. The Lancet Neurology, 1, 97–109. doi: http://dx.doi.org/10.1016/S1474-4422(07)70327-7.

Kryzhanovskij, G. N., Karaban, I. N., Magaeva, S. V., Kucheryanu, V. G., & Karaban, N. V. (2002) Bolezn´ Parkinsona (e´tiologiya, patogenez, klinika, diagnostika, lechenie, profilaktika) [Parkinson's Disease (etiology, pathogenesis, clinical manifestations, diagnosis, treatment, prevention)]. Moscow: Medicina. [in Russian].

How to Cite

1.
Kutsak А, Buchakchyiska NM. Modern views on etiology and pathogenesis of Parkinson’s disease. Zaporozhye Medical Journal [Internet]. 2016Dec.8 [cited 2024Nov.2];18(6). Available from: http://zmj.zsmu.edu.ua/article/view/85533